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Hemophilus influenzae b) and T-independent (23-valent pneumococcal polysaccharide) vaccines. For the most part, the pattern of immunodeficiency seen in an A–T patient early in life (by age five) will be the same pattern seen throughout the lifetime of that individual. Therefore, the tests need not be repeated unless that individual develops more problems with infection. Problems with immunity sometimes can be overcome by immunization. Vaccines against common bacterial respiratory pathogens such as
Hemophilus influenzae, pneumococci and influenza virus (the "flu") are commercially available and often help to boost antibody responses, even in individuals with low immunoglobulin levels. If the vaccines do not work and the patient continues to have problems with infections, gamma globulin therapy (IV or subcutaneous infusions of antibodies collected from normal individuals) may be of benefit. A small number of people with A–T develop an abnormality in which one or more types of immunoglobulin are increased far beyond the normal range. In a few cases, the immunoglobulin levels can be increased so much that the blood becomes thick and does not flow properly. Therapy for this problem must be tailored to the specific abnormality found and its severity.
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managed with prophylactic antibiotics and minimized exposure to infection. If antibody function is normal, all routine childhood immunizations including live viral vaccines (measles, mumps, rubella and varicella) should be given. In addition, several "special" vaccines (that is, licensed but not routine for otherwise healthy children and young adults) should be given to decrease the risk that an A–T patient will develop lung infections. The patient and all household members should receive the influenza (flu) vaccine every fall. People with A–T who are less than two years old should receive three doses of a pneumococcal conjugate vaccine (Prevnar) given at two month intervals. People older than two years who have not previously been immunized with
Prevnar should receive two doses of Prevnar. At least 6 months after the last Prevnar has been given and after the child is at least two years old, the 23-valent pneumococcal vaccine should be administered. Immunization with the 23-valent pneumococcal vaccine should be repeated approximately every five years after the first dose.
711:(CP) describes a non-progressive disorder of motor function stemming from malformation or early damage to the brain. CP can manifest in many ways, given the different manner in which the brain can be damaged; in common to all forms is the emergence of signs and symptoms of impairment as the child develops. However, milestones that have been accomplished and neurologic functions that have developed do not deteriorate in CP as they often do in children with A–T in the late pre-school years. Most children with ataxia caused by CP do not begin to walk at a normal age, whereas most children with A–T start to walk at a normal age even though they often "wobble" from the start. Pure ataxia is a rare manifestation of early brain damage or malformation, however, and the possibility of an occult genetic disorder of brain should be considered and sought for those in whom ataxia is the chief manifestation of CP. Children with ataxic CP will not manifest the laboratory abnormalities associated with A–T.
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text that is read to them. Delays in speech initiation and lack of facial expression make it seem that they do not know the answers to questions. Reduction of the skilled effort needed to answer questions, and an increase of the time available to respond, is often rewarded by real accomplishment. It is important to recognize that intellectual disability is not regularly a part of the clinical picture of A–T although school performance may be suboptimal because of the many difficulties in reading, writing, and speech. Children with A–T are often very conscious of their appearance, and strive to appear normal to their peers and teachers. Life within the ataxic body can be tiring. The enhanced effort needed to maintain appearances and increased energy expended in abnormal tone and extra movements all contribute to physical and mental fatigue. As a consequence, for some a shortened school day yields real benefits.
887:(greater than 7 days), even following what was presumed to have been a viral infection. To help prevent respiratory illnesses from common respiratory pathogens, annual influenza vaccinations should be given and pneumococcal vaccines should be administered when appropriate. Antibiotic treatment should also be considered in children with chronic coughs that are productive of mucous, those who do not respond to aggressive pulmonary clearance techniques and in children with muco-purulent secretions from the sinuses or chest. A wet cough can also be associated with chronic aspiration which should be ruled out through proper diagnostic studies, however, aspiration and respiratory infections are not necessarily exclusive of each other. In children and adults with bronchiectasis, chronic antibiotic therapy should be considered to slow chronic lung disease progression.
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risk for infection. Such individuals develop complications from live viral vaccines (measles, mumps, rubella and chickenpox), chronic or severe viral infections, yeast infections of the skin and vagina, and opportunistic infections (such as pneumocystis pneumonia). Although lymphocyte counts are often as low in people with A–T, they seldom have problems with opportunistic infections. (The one exception to that rule is that problems with chronic or recurrent warts are common.) The number and function of T-lymphocytes should be re-evaluated if a person with A–T is treated with corticosteroid drugs such as prednisone for longer than a few weeks or is treated with chemotherapy for cancer. If lymphocyte counts are low in people taking those types of drugs, the use of prophylactic antibiotics is recommended to prevent opportunistic infections.
272:(IgA, IgM, and IgG subclasses), not making antibodies in response to vaccines or infections, and having low numbers of lymphocytes (especially T-lymphocytes) in the blood. Some people have frequent infections of the upper (colds, sinus and ear infections) and lower (bronchitis and pneumonia) respiratory tract. All children with A–T should have their immune systems evaluated to detect those with severe problems that require treatment to minimize the number or severity of infections. Some people with A–T need additional immunizations (especially with pneumonia and influenza vaccines), antibiotics to provide protection (prophylaxis) from infections, and/or infusions of immunoglobulins (gamma globulin). The need for these treatments should be determined by an expert in the field of immunodeficiency or infectious diseases.
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938:), abnormalities of eye control (oculomotor apraxia), and impaired fine motor control. Despite these problems, children with A–T often enjoy school if proper accommodations to their disability can be made. The decision about the need for special education classes or extra help in regular classes is highly influenced by the local resources available. Decisions about proper educational placement should be revisited as often as circumstances warrant. Despite their many neurologic impairments, most individuals with A–T are very socially aware and socially skilled, and thus benefit from sustained peer relationships developed at school. Some individuals are able to function quite well despite their disabilities and a few have graduated from community colleges.
260:) of the eyes usually occur by the age of 5–8 years, but sometimes appear later or not at all. The absence of telangiectasia does not exclude the diagnosis of A–T. Potentially a cosmetic problem, the ocular telangiectasia do not bleed or itch, though they are sometimes misdiagnosed as chronic conjunctivitis. It is their constant nature, not changing with time, weather or emotion, that marks them as different from other visible blood vessels. Telangiectasia can also appear on sun-exposed areas of skin, especially the face and ears. They occur in the bladder as a late complication of chemotherapy with cyclophosphamide, have been seen deep inside the brain of older people with A–T, and occasionally arise in the liver and lungs.
206:. The diagnosis of A–T may not be made until the preschool years when the neurologic symptoms of impaired gait, hand coordination, speech and eye movement appear or worsen, and the telangiectasia first appear. Because A–T is so rare, doctors may not be familiar with the symptoms, or methods of making a diagnosis. The late appearance of telangiectasia may be a barrier to the diagnosis. It may also take some time before doctors consider A–T as a possibility because of the early stability of symptoms and signs. There are patients who have been diagnosed with A-T only in adulthood due to an attenuated form of the disease, and this has been correlated with the type of their gene mutation.
487:, the gene responsible for this multi-system disorder, encodes a protein of the same name which coordinates the cellular response to DNA double strand breaks (DSBs). Radiation therapy, chemotherapy that acts like radiation (radiomimetic drugs) and certain biochemical processes and metabolites can cause DSBs. When these breaks occur, ATM stops the cell from making new DNA (cell cycle arrest) and recruits and activates other proteins to repair the damage. Thus, ATM allows the cell to repair its DNA before the completion of cell division. If DNA damage is too severe, ATM will mediate the process of programmed cell death (apoptosis) to eliminate the cell and prevent genomic instability.
765:(AOA1) is an autosomal recessive disorder similar to A–T in manifesting increasing problems with coordination and oculomotor apraxia, often at a similar age to those having A–T. It is caused by mutation in the gene coding for the protein aprataxin. Affected individuals differ from those with A–T by the early appearance of peripheral neuropathy, early in their course manifest difficulty with initiation of gaze shifts, and the absence of ocular telangiectasia, but laboratory features are of key importance in the differentiation of the two. Individuals with AOA1 have a normal AFP, normal measures of immune function, and after 10–15 years have low serum levels of albumin.
789:(NBS) is a rare genetic disorder that has similar chromosomal instability to that seen in people with A–T, but the problems experienced are quite different. Children with NBS have significant microcephaly, a distinct facial appearance, short stature, and moderate cognitive impairment, but do not experience any neurologic deterioration over time. Like those with A–T, children with NBS have enhanced sensitivity to radiation, disposition to lymphoma and leukemia, and some laboratory measures of impaired immune function, but do not have ocular telangiectasia or an elevated level of
249:
721:(FA) is the most common genetic cause of ataxia in children. Like A–T, FA is a recessive disease, appearing in families without a history of the disorder. FA is caused by mutation in the frataxin gene, most often an expansion of a naturally occurring repetition of the three nucleotide bases GAA from the usual 5–33 repetitions of this trinucleotide sequence to greater than 65 repeats on each chromosome. Most often the ataxia appears between 10 and 15 years of age, and differs from A–T by the absence of telangiectasia and oculomotor apraxia, a normal
775:(AOA2) is an autosomal recessive disorder also similar to A–T in manifesting increasing problems with coordination and peripheral neuropathy, but oculomotor apraxia is present in only half of affected individuals. Ocular telangiectasia do not develop. Laboratory abnormalities of AOA2 are like A–T, and unlike AOA1, in having an elevated serum AFP level, but like AOA1 and unlike A–T in having normal markers of immune function. Genetic testing of the senataxin gene (SETX) can confirm the diagnosis. There is no enhanced risk for cancer.
476:
2790:
895:
physiotherapy vest. Chest physiotherapy can help bring up mucous from the lower bronchial tree, however, an adequate cough is needed to remove secretions. In people who have decreased lung reserve and a weak cough, use of an insufflator-exsufflator (cough-assist) device may be useful as a maintenance therapy or during acute respiratory illnesses to help remove bronchial secretions from the upper airways. Evaluation by a
Pulmonology specialist, however, should first be done to properly assess patient suitability.
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those with A–T by the absence of telangiectasia, normal immunoglobulin levels, a later onset, and a slower progression of the symptoms. Because of its rarity, it is not yet known whether or not ATLD carries an increased risk to develop cancer. Because those mutations of Mre11 that severely impair the MRE11 protein are incompatible with life, individuals with ATLD all have some partial function of the Mre11 protein, and hence likely all have their own levels of disease severity.
518:
428:
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lymphocytes and some impairment of lymphocyte function (such as an impaired ability to make antibodies in response to vaccines or infections). In addition, broken pieces of DNA in chromosomes involved in the above-mentioned rearrangements have a tendency to recombine with other genes (translocation), making the cells prone to the development of cancer (lymphoma and leukemia).
725:, and the frequent presence of scoliosis, absent tendon reflexes, and abnormal features on the EKG. Individuals with FA manifest difficulty standing in one place that is much enhanced by closure of the eyes (Romberg sign) that is not so apparent in those with A–T – even though those with A–T may have greater difficulty standing in one place with their eyes open.
215:
becomes more difficult, and children will use doorways and walls for support. Children with A–T often appear better when running or walking quickly in comparison to when they are walking slowly or standing in one place. Around the beginning of their second decade, children with the more severe ("classic") form of A–T start using a
715:
infancy and toddler years, and mostly improves with time. This contrasts to the oculomotor difficulties evident in children with A–T, which are not evident in early childhood but emerge over time. Cogan's oculomotor apraxia is generally an isolated problem, or may be associated with broader developmental delay.
450:. Each parent is a carrier, meaning that they have one normal copy of the A–T gene (ATM) and one copy that is mutated. A–T occurs if a child inherits the mutated A–T gene from each parent, so in a family with two carrier parents, there is 1 chance in 4 that a child born to the parents will have the disorder.
573:(located exclusively in the cerebellum). The cause of this cell loss is not known, though many hypotheses have been proposed based on experiments performed both in cell culture and in the mouse model of A–T. Current hypotheses explaining the neurodegeneration associated with A–T include the following:
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Many of the problems encountered will benefit from special attention, as problems are often related more to "input and output" issues than to intellectual impairment. Problems with eye movement control make it difficult for people with A–T to read, yet most fully understand the meaning and nuances of
873:
In people with A–T who have low levels of IgA, further testing should be performed to determine whether the IgA level is low or completely absent. If absent, there is a slightly increased risk of a transfusion reaction. "Medical Alert" bracelets are not necessary, but the family and primary physician
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People with A–T have an increased sensitivity to ionizing radiation (X-rays and gamma rays). Therefore, X-ray exposure should be limited to times when it is medically necessary, as exposing an A–T patient to ionizing radiation can damage cells in such a way that the body cannot repair them. The cells
622:
These hypotheses may not be mutually exclusive and more than one of these mechanisms may underlie neuronal cell death when there is an absence or deficiency of ATM. Further, cerebellar damage and loss of
Purkinje and granule cells do not explain all of the neurologic abnormalities seen in people with
327:
Involuntary movements may make feeding difficult or messy and may excessively prolong mealtimes. It may be easier to finger feed than use utensils (e.g., spoon or fork). For liquids, it is often easier to drink from a closed container with a straw than from an open cup. Caregivers may need to provide
214:
The first indications of A–T usually occur during the toddler years. Children start walking at a normal age, but may not improve much from their initial wobbly gait. Sometimes they have problems standing or sitting still and tend to sway backward or from side to side. In primary school years, walking
125:
gene, named after this disease, which is involved in the recognition and repair of damaged DNA. Heterozygotes will not experience the characteristic symptoms but it has been reported they have higher risks of cancer and heart disease. The prevalence of A–T is estimated to be as high as 1 in 40,000 to
1955:
Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N, et al. (Breast Cancer
Susceptibility Collaboration, (UK)) (August 2006). "ATM mutations that cause ataxia–telangiectasia are
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Physical therapy is useful to maintain strength and general cardiovascular health. Horseback therapy and exercises in a swimming pool are often well tolerated and fun for people with A–T. However, no amount of practice will slow the cerebellar degeneration or improve neurologic function. Exercise to
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studying the use of red blood cells (erythrocytes) loaded with dexamethasone sodium phosphate found that this treatment improved symptoms and appeared to be well tolerated. This treatment uses a unique delivery system for medication by using the patient's own red blood cells as the delivery vehicle
890:
Culturing of the sinuses may be needed to direct antibiotic therapy. This can be done by an Ear Nose and Throat (ENT) specialist. In addition, diagnostic bronchoscopy may be necessary in people who have recurrent pneumonias, especially those who do not respond or respond incompletely to a course of
869:
If the tests show significant abnormalities of the immune system, a specialist in immunodeficiency or infectious diseases will be able to discuss various treatment options. Absence of immunoglobulin or antibody responses to vaccine can be treated with replacement gamma globulin infusions, or can be
865:
Most people with A–T have low lymphocyte counts in the blood. This problem seems to be relatively stable with age, but a rare number of people do have progressively decreasing lymphocyte counts as they get older. In the general population, very low lymphocyte counts are associated with an increased
853:
If an individual patient's susceptibility to infection increases, it is important to reassess immune function in case deterioration has occurred and a new therapy is indicated. If infections are occurring in the lung, it is also important to investigate the possibility of dysfunctional swallow with
714:
Cogan occulomotor apraxia is a rare disorder of development. Affected children have difficulty moving their eyes only to a new visual target, so they will turn their head past the target to "drag" the eyes to the new object of interest, then turn the head back. This tendency becomes evident in late
508:
Infertility is often described as a characteristic of A–T. Whereas this is certainly the case for the mouse model of A–T, in humans it may be more accurate to characterize the reproductive abnormality as gonadal atrophy or dysgenesis characterized by delayed pubertal development. Because programmed
957:
Speech-language pathologists may facilitate communication skills that enable persons with A–T to get their messages across (using key words vs. complete sentences) and teach strategies to decrease frustration associated with the increase time needed to respond to questions (e.g., holding up a hand
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gene, that could be considered in the differential diagnosis of A–T. Patients with ATLD are very similar to those with A–T in showing a progressive cerebellar ataxia, hypersensitivity to ionizing radiation and genomic instability. Those rare individuals with ATLD who are well described differ from
534:
Cells from people with A–T demonstrate genomic instability, slow growth and premature senescence in culture, shortened telomeres and an ongoing, low-level stress response. These factors may contribute to the progeric (signs of early aging) changes of skin and hair sometimes observed in people with
525:
As lymphocytes develop from stem cells in the bone marrow into mature lymphocytes in the periphery, they rearrange special segments of their DNA . This process requires them to make DSBs, which are difficult to repair in the absence of ATM. As a result, most people with A–T have reduced numbers of
219:
for long distances. During school years, children may have increasing difficulty with reading because of impaired coordination of eye movement. At the same time, other problems with fine-motor functions (writing, coloring, and using utensils to eat), and with speech (dysarthria) may arise. Most of
898:
Children and adults with chronic dry cough, increased work of breathing (fast respiratory rate, shortness of breath at rest or with activities) and absence of an infectious process to explain respiratory symptoms should be evaluated for interstitial lung disease or another intrapulmonary process.
886:
Recurrent sinus and lung infections can lead to the development of chronic lung disease. Such infections should be treated with appropriate antibiotics to prevent and limit lung injury. Administration of antibiotics should be considered when children and adults have prolonged respiratory symptoms
677:
The diagnosis can be confirmed in the laboratory by finding an absence or deficiency of the ATM protein in cultured blood cells, an absence or deficiency of ATM function (kinase assay), or mutations in both copies of the cell's ATM gene. These more specialized tests are not always needed, but are
461:
Carriers of A–T, such as the parents of a person with A–T, have one mutated copy of the ATM gene and one normal copy. They are generally healthy, but there is an increased risk of breast cancer in women. This finding has been confirmed in a variety of different ways, and is the subject of current
339:
is common because of the neurological changes that interfere with coordination of mouth and pharynx (throat) movements that are needed for safe and efficient swallowing. Coordination problems involving the mouth may make chewing difficult and increase the duration of meals. Problems involving the
83:
Symptoms most often first appear in early childhood (the toddler stage) when children begin to sit or walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting. In late pre-school and early school age, they develop difficulty moving their
457:
Looking for mutations in the ATM gene of an unrelated person (for example, the spouse of a known A–T carrier) presents significant challenges. Genes often have variant spellings (polymorphisms) that do not affect function. In a gene as large as ATM, such variant spellings are likely to occur and
907:
Oral intake may be aided by teaching persons with A–T how to drink, chew and swallow more safely. The propriety of treatments for swallowing problems should be determined following evaluation by an expert in the field of speech-language pathology. Dieticians may help treat nutrition problems by
1197:
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M,
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foods or liquids so that self-feeding is possible, or they may need to feed the person with A–T. In general, meals should be completed within approximately 30 minutes. Longer meals may be stressful, interfere with other daily activities, and limit the intake of necessary liquids and nutrients.
849:
All individuals with A–T should have at least one comprehensive immunologic evaluation that measures the number and type of lymphocytes in the blood (T-lymphocytes and B-lymphocytes), the levels of serum immunoglobulins (IgG, IgA, and IgM) and antibody responses to T-dependent (e.g., tetanus,
827:
Differentiation of these disorders is often possible with clinical features and selected laboratory tests. In cases where the distinction is unclear, clinical laboratories can identify genetic abnormalities of ATM, aprataxin and senataxin, and specialty centers can identify abnormality of the
418:
Many individuals with A–T develop deformities of the feet that compound the difficulty they have with walking due to impaired coordination. Early treatment may slow progression of this deformity. Bracing or surgical correction sometimes improves stability at the ankle sufficient to enable an
291:
Women who are A–T carriers (who have one mutated copy of the ATM gene), have approximately a two-fold increased risk for the development of breast cancer compared to the general population. This includes all mothers of A–T children and some female relatives. Current consensus is that special
894:
Clearance of bronchial secretions is essential for good pulmonary health and can help limit injury from acute and chronic lung infections. Children and adults with increased bronchial secretions can benefit from routine chest therapy using the manual method, an a cappella device or a chest
877:
People with A–T also have an increased risk of developing autoimmune or chronic inflammatory diseases. This risk is probably a secondary effect of their immunodeficiency and not a direct effect of the lack of ATM protein. The most common examples of such disorders in A–T include immune
555:
levels after the age of two, and measured levels of AFP appear to increase slowly over time. AFP levels are very high in the newborn, and normally descend to adult levels over the first year to 18 months. The reason why individuals with A–T have elevated levels of AFP is not yet known.
100:). Because not all children develop in the same manner or at the same rate, it may be some years before A–T is properly diagnosed. Most children with A–T have stable neurologic symptoms for the first 4–5 years of life, but begin to show increasing problems in early school years.
640:
The diagnosis of A–T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated
315:
Lung function tests (spirometry) should be performed at least annually in children old enough to perform them, influenza and pneumococcal vaccines given to eligible individuals, and sinopulmonary infections treated aggressively to limit the development of chronic lung disease.
899:
Evaluation by a
Pulmonologist and a CT scan of the chest should be considered in individuals with symptoms of interstitial lung disease or to rule other non-infectious pulmonary processes. People diagnosed with interstitial lung disease may benefit from systemic steroids.
220:
these neurologic problems stop progressing after the age of about 12 – 15 years, though involuntary movements may start at any age and may worsen over time. These extra movements can take many forms, including small jerks of the hands and feet that look like fidgeting (
986:
Social interactions with peers are important, and should be taken into consideration for class placement. For everyone long-term peer relationships can be the most rewarding part of life; for those with A–T establishing these connections in school years can be
462:
research. Standard surveillance (including monthly breast self-exams and mammography at the usual schedule for age) is recommended, unless additional tests are indicated because the individual has other risk factors (e.g., family history of breast cancer).
454:(and carrier detection) can be carried out in families if the errors (mutation) in an affected child's two ATM genes have been identified. The process of getting this done can be complicated and, as it requires time, should be arranged before conception.
419:
individual to walk with support, or bear weight during assisted standing transfers from one seat to another. Severe scoliosis is relatively uncommon, but probably does occur more often than in those without A–T. Spinal fusion is only rarely indicated.
304:(an auto-immune disease causing loss of skin pigment resulting in a blotchy "bleach-splashed" look), and warts which can be extensive and recalcitrant to treatment. A small number of people develop a chronic inflammatory skin disease (granulomas).
5011:
4996:
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A–T. For example, DNA damage and genomic instability cause melanocyte stem cell (MSC) differentiation which produces graying. Thus, ATM may be a "stemness checkpoint" protecting against MSC differentiation and premature graying of the hair.
458:
doctors cannot always predict whether a specific variant will or will not cause disease. Genetic counseling can help family members of an A–T patient understand what can or cannot be tested, and how the test results should be interpreted.
648:
A variety of laboratory abnormalities occur in most people with A–T, allowing for a tentative diagnosis to be made in the presence of typical clinical features. Not all abnormalities are seen in all patients. These abnormalities include:
564:
A–T is one of several DNA repair disorders that result in neurological abnormalities or degeneration. Arguably some of the most devastating symptoms of A–T are a result of progressive cerebellar degeneration, characterized by the loss of
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Chessa L, Leuzzi V, Plebani A, Soresina A, Micheli R, D'Agnano D, Venturi T, Molinaro A, Fazzi E, Marini M, Ferremi Leali P, Quinti I, Cavaliere FM, Girelli G, Pietrogrande MC, Finocchi A, Tabolli S, Abeni D, Magnani M (January 2014).
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Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wakayama T, Iseki S, Hara E, Masunaga T, Shimizu H, Nishimura EK (June 2009). "Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation".
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may not cough when they aspirate (silent aspiration). Swallowing problems and especially swallowing problems with silent aspiration may cause lung problems due to inability to cough and clear food and liquids from the airway.
157:(dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. These are not apparent in infancy and may first appear at age 5–8 years. Telangiectasia may also appear on sun-exposed areas of skin.
6684:
3078:
Bredemeyer AL, Helmink BA, Innes CL, Calderon B, McGinnis LM, Mahowald GK, Gapud EJ, Walker LM, Collins JB, Weaver BK, Mandik-Nayak L, Schreiber RD, Allen PM, May MJ, Paules RS, Bassing CH, Sleckman BP (December 2008).
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Bredemeyer AL, Sharma GG, Huang CY, Helmink BA, Walker LM, Khor KC, Nuskey B, Sullivan KE, Pandita TK, Bassing CH, Sleckman BP (July 2006). "ATM stabilizes DNA double-strand-break complexes during V(D)J recombination".
1018:(EMA) for the treatment of various genetic diseases, including Ataxia-Telangiectasia. N-Acetyl-Leucine has also been granted Orphan Drug Designations in the US and EU for related inherited cerebellar ataxias, such as
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and informing others about the need to allow more time for responses). Rarely helpful are traditional speech therapies that focus on the production of specific sounds and strengthening of the lip and tongue muscles.
509:
DSBs are generated to initiate genetic recombinations involved in the production of sperm and eggs in reproductive organs (a process known as meiosis), meiotic defects and arrest can occur when ATM is not present.
2037:
McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, Brody AS, Langston C, Fan LL, Lefton-Greif MA, Crawford TO, Troche M, Sandlund JT, Auwaerter PG, Easley B, Loughlin GM, Carroll JL, Lederman HM (September 2010).
495:
In the absence of the ATM protein, cell-cycle check-point regulation and programmed cell death in response to DSBs are defective. The result is genomic instability which can lead to the development of cancers.
6259:
499:
Irradiation and radiomimetic compounds induce DSBs which are unable to be repaired appropriately when ATM is absent. Consequently, such agents can prove especially cytotoxic to A–T cells and people with A–T.
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443:(ATM serine/threonine kinase or ataxia–telangiectasia mutated) gene, which was cloned in 1995. ATM is located on human chromosome 11 (11q22.3) and is made up of 69 exons spread across 150kb of genomic DNA.
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Chun HH, Sun X, Nahas SA, Teraoka S, Lai CH, Concannon P, Gatti RA (December 2003). "Improved diagnostic testing for ataxia–telangiectasia by immunoblotting of nuclear lysates for ATM protein expression".
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Classroom aides may be appropriate, especially to help with scribing, transportation through the school, mealtimes and toileting. The impact of an aide on peer relationships should be monitored carefully.
686:
There are several other disorders with similar symptoms or laboratory features that physicians may consider when diagnosing A–T. The three most common disorders that are sometimes confused with A–T are:
134:
There is substantial variability in the severity of features of A–T among affected individuals, and at different ages. The following symptoms or problems are either common or important features of A–T:
824:
kinase. Thus, the similarity of the three diseases can be explained in part by the fact that the protein products of the three genes mutated in these disorders interact in common pathways in the cell.
4179:
Sun X, Becker-Catania SG, Chun HH, Hwang MJ, Huo Y, Wang Z, Mitui M, Sanal O, Chessa L, Crandall B, Gatti RA (June 2002). "Early diagnosis of ataxia–telangiectasia using radiosensitivity testing".
6677:
5984:
5979:
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levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person's ATM genes).
5996:
5974:
2157:
Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K (December 1988). "Localization of an ataxia–telangiectasia gene to chromosome 11q22-23".
2087:
Lefton-Greif MA, Crawford TO, Winkelstein JA, Loughlin GM, Koerner CB, Zahurak M, Lederman HM (February 2000). "Oropharyngeal dysphagia and aspiration in patients with ataxia–telangiectasia".
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Shiloh Y, Tabor E, Becker Y (July 1982). "Colony-forming ability of ataxia–telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors".
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is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United
Kingdom).
6955:
5147:
3136:
Callén E, Jankovic M, Difilippantonio S, Daniel JA, Chen HT, Celeste A, Pellegrini M, McBride K, Wangsa D, Bredemeyer AL, Sleckman BP, Ried T, Nussenzweig M, Nussenzweig A (July 2007).
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Louis-Bar D (1941). "Sur un syndrome progressif cormprenant des télangiectasies capillaires cutanées et conjonctivales symétriques, à disposition naevoïde et des troubles cérébelleux".
828:
proteins of potentially responsible genes, such as ATM, MRE11, nibrin, TDP1, aprataxin and senataxin as well as other proteins important to ATM function such as ATR, DNA-PK, and RAD50.
6670:
1505:
van Os NJ, Chessa L, Weemaes CM, van Deuren M, Fiévet A, van Gaalen J, Mahlaoui N, Roeleveld N, Schrader C, Schindler D, Taylor AM, Van de
Warrenburg BP, Dörk T, Willemsen MA (2019).
6252:
951:
All children with A–T need special attention to the barriers they experience in school. In the United States, this takes the form of a formal IEP (Individualized
Education Program).
3350:
Herzog KH, Chong MJ, Kapsetaki M, Morgan JI, McKinnon PJ (May 1998). "Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system".
728:
There are other rare disorders that can be confused with A–T, either because of similar clinical features, a similarity of some laboratory features, or both. These include:
1999:
Paller AS, Massey RB, Curtis MA, Pelachyk JM, Dombrowski HC, Leickly FE, Swift M (December 1991). "Cutaneous granulomatous lesions in patients with ataxia–telangiectasia".
1865:
Reiman A, Srinivasan V, Barone G, Last JI, Wootton LL, Davies EG, Verhagen MM, Willemsen MA, Weemaes CM, Byrd PJ, Izatt L, Easton DF, Thompson DJ, Taylor AM (August 2011).
4718:
6245:
5343:
3274:
Stray-Pedersen A, Borresen-Dale AL, Paus E, Lindman CR, Burgers T, Abrahamsen TG (November 2007). "Alpha fetoprotein is increasing with age in ataxia–telangiectasia".
1151:
1415:"ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer"
6960:
2702:
Plug AW, Peters AH, Xu Y, Keegan KS, Hoekstra MF, Baltimore D, de Boer P, Ashley T (December 1997). "ATM and RPA in meiotic chromosome synapsis and recombination".
1639:
Crawford TO, Mandir AS, Lefton-Greif MA, Goodman SN, Goodman BK, Sengul H, Lederman HM (April 2000). "Quantitative neurologic assessment of ataxia–telangiectasia".
754:
5338:
6950:
5140:
3442:
Sordet O, Redon CE, Guirouilh-Barbat J, Smith S, Solier S, Douarre C, Conti C, Nakamura AJ, Das BB, Nicolas E, Kohn KW, Bonner WM, Pommier Y (August 2009).
3395:"Ataxia telangiectasia mutated-dependent apoptosis after genotoxic stress in the developing nervous system is determined by cellular differentiation status"
874:
should be aware that if there is elective surgery requiring red cell transfusion, the cells should be washed to decrease the risk of an allergic reaction.
6477:
6325:
6160:
4743:
Strupp M, Bayer O, Feil K, Straube A (February 2019). "Prophylactic treatment of migraine with and without aura with acetyl-DL-leucine: a case series".
3581:
Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL (March 2010).
3542:"Increased chromosome instability dramatically disrupts neural genome integrity and mediates cerebellar degeneration in the ataxia–telangiectasia brain"
1771:
Rothblum-Oviatt, Cynthia; Wright, Jennifer; Lefton-Greif, Maureen A.; McGrath-Morrow, Sharon A.; Crawford, Thomas O.; Lederman, Howard M. (2016-11-25).
1413:
Stankovic T, Kidd AM, Sutcliffe A, McGuire GM, Robinson P, Weber P, Bedenham T, Bradwell AR, Easton DF, Lennox GG, Haites N, Byrd PJ, Taylor AM (1998).
2852:
Franco S, Alt FW, Manis JP (September 2006). "Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations".
1094:
Individuals of all races and ethnicities are affected equally. The incidence worldwide is estimated to be between 1 in 40,000 and 1 in 100,000 people.
1033:
Published case series studies have demonstrated the positive clinical benefit of treatment with N-Acetyl-Leucine various inherited cerebellar ataxias.
6930:
6818:
6514:
5966:
1867:"Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours"
88:). They develop slurred or distorted speech, and swallowing problems. Some have an increased number of respiratory tract infections (ear infections,
6206:
1462:
Dörk T, Bendix-Waltes R, Wegner RD, Stumm M (2004). "Slow progression of ataxia-telangiectasia with double missense and in frame splice mutations".
268:
About two-thirds of people with A–T have abnormalities of the immune system. The most common abnormalities are low levels of one or more classes of
1370:
Cabana MD, Crawford TO, Winkelstein JA, Christensen JR, Lederman HM (July 1998). "Consequences of the delayed diagnosis of ataxia–telangiectasia".
399:
Control of eye movement is often impaired, affecting visual functions that require fast, accurate eye movements from point to point (e.g. reading).
5956:
5133:
934:
Most children with A–T have difficulty in school because of a delay in response time to visual, verbal or other cues, slurred and quiet speech (
632:
can cope normally with other forms of radiation, such as ultraviolet light, so there is no need for special precautions from sunlight exposure.
6641:
6077:
5936:
5609:
1830:
Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM (April 2004). "Immunodeficiency and infections in ataxia–telangiectasia".
6343:
5961:
5593:
2887:
Callén E, Jankovic M, Wong N, Zha S, Chen HT, Difilippantonio S, Di
Virgilio M, Heidkamp G, Alt FW, Nussenzweig A, Nussenzweig M (May 2009).
812:
complex, plays an important role in DNA damage repair and signaling and is required to recruit ATM to the sites of DNA double strand breaks.
772:
762:
738:
732:
6945:
6226:
5799:
5787:
5249:
4849:"Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial"
2803:
Lumsden JM, McCarty T, Petiniot LK, Shen R, Barlow C, Wynn TA, Morse HC, Gearhart PJ, Wynshaw-Boris A, Max EE, Hodes RJ (November 2004).
2122:
Farr AK, Shalev B, Crawford TO, Lederman HM, Winkelstein JA, Repka MX (December 2002). "Ocular manifestations of ataxia–telangiectasia".
6646:
5026:
2352:"ATM, the Mre11/Rad50/Nbs1 complex, and topoisomerase I are concentrated in the nucleus of Purkinje neurons in the juvenile human brain"
2653:
Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A (July 1996).
6018:
5951:
5506:
2515:
Bakkenist CJ, Kastan MB (January 2003). "DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation".
1023:
1011:
6725:
5721:
5524:
1275:
6779:
3311:"Nuclear ataxia–telangiectasia mutated (ATM) mediates the cellular response to DNA double strand breaks in human neuron-like cells"
3031:"Aberrant V(D)J recombination in ataxia telangiectasia mutated-deficient lymphocytes is dependent on nonhomologous DNA end joining"
1040:
6581:
6905:
6498:
6409:
4122:"A novel role for ATM in regulating proteasome-mediated protein degradation through suppression of the ISG15 conjugation pathway"
2402:
Valentin-Vega YA, Maclean KH, Tait-Mulder J, Milasta S, Steeves M, Dorsey FC, Cleveland JL, Green DR, Kastan MB (February 2012).
4722:
6828:
5840:
3689:
Biton S, Barzilai A, Shiloh Y (July 2008). "The neurological phenotype of ataxia–telangiectasia: solving a persistent puzzle".
623:
A–T. The effects of ATM deficiency on the other areas of the brain outside of the cerebellum are being actively investigated.
6965:
6701:
6651:
6521:
6393:
5355:
5331:
5161:
4069:"Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency"
996:
No curative medication has been approved for the treatment of inherited cerebellar ataxias, including Ataxia-Telangiectasia.
6884:
6107:
5547:
4953:
4515:
4491:
4467:
4442:
954:
Children with A–T tend to be excellent problem solvers. Their involvement in how to best perform tasks should be encouraged.
6034:
5919:
5835:
5777:
5326:
1060:
821:
248:
6388:
6165:
483:
A–T has been described as a genome instability syndrome, a DNA repair disorder and a DNA damage response (DDR) syndrome.
6662:
6003:
5377:
4967:
1548:"Severe reaction to radiotherapy provoked by hypomorphic germline mutations in ATM (ataxia-telangiectasia mutated gene)"
670:
Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes)
6134:
1036:
A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment Ataxia-Telangiectasia began in 2019.
6693:
6501:
6353:
6320:
6145:
5513:
1103:
440:
120:
6221:
2263:
Kurz EU, Lees-Miller SP (Aug–Sep 2004). "DNA damage-induced activation of ATM and ATM-dependent signaling pathways".
1507:"Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576G>A and c.8147T>C mutations"
6851:
6806:
6767:
6070:
5991:
5541:
5213:
786:
747:
6102:
6487:
6382:
6377:
6372:
6367:
6362:
6297:
6190:
5941:
5909:
5861:
5710:
5289:
3444:"Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks"
1027:
1015:
50:
6900:
2938:"Regulation of oxidative stress responses by ataxia–telangiectasia mutated is required for T cell proliferation"
61:
to small dilated blood vessels, both of which are hallmarks of the disease. A–T affects many parts of the body:
6536:
6284:
6185:
6008:
5782:
5196:
5037:
1198:
Collins FS, Shiloh Y (June 1995). "A single ataxia telangiectasia gene with a product similar to PI-3 kinase".
475:
6823:
6013:
2747:"ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes"
6237:
4540:
280:
People with A–T have a highly increased incidence (approximately 25% lifetime risk) of cancers, particularly
6970:
6935:
6636:
6621:
6617:
5946:
5702:
5520:
5372:
5362:
5206:
2789:
6746:
6216:
6130:
5878:
5870:
5825:
5501:
5473:
5321:
2889:"Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes"
1064:
1019:
718:
696:
584:
3726:"Reducing mitochondrial ROS improves disease-related pathology in a mouse model of ataxia–telangiectasia"
2303:"Analysis of the ataxia telangiectasia mutated-mediated DNA damage response in murine cerebellar neurons"
1048:
968:
Hearing is normal throughout life. Books on tape may be a useful adjunct to traditional school materials.
543:
The cause of telangiectasia or dilated blood vessels in the absence of the ATM protein is not yet known.
6789:
6611:
6591:
6312:
6211:
6063:
5893:
5767:
5585:
5563:
5478:
5401:
5311:
5298:
5223:
5113:
1145:
4972:
4962:
1914:
Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF (June 2005).
983:
Like all children, those with A–T need to have goals to experience the satisfaction of making progress.
980:
Allow rest time, shortened days, reduced class schedule, reduced homework, modified tests as necessary.
758:
Comparison of clinical and laboratory features of rare genetic disorders than can be confused with A–T
6631:
6335:
5830:
5647:
5536:
4133:
3922:"Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia"
3594:
3359:
3092:
2987:
2524:
2463:
2454:
Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT (October 2010). "ATM activation by oxidative stress".
2166:
1259:
1247:
1207:
804:(defective in NBS) genes exist in the cell as a complex, along with a third protein expressed by the
778:
Ataxia–telangiectasia like disorder (ATLD) is an extremely rare condition, caused by mutation in the
148:(difficulty with coordination of head and eye movement when shifting gaze from one place to the next)
4564:
Strupp M, Teufel J, Habs M, Feuerecker R, Muth C, van de Warrenburg BP, et al. (October 2013).
3491:
Das BB, Antony S, Gupta S, Dexheimer TS, Redon CE, Garfield S, Shiloh Y, Pommier Y (December 2009).
595:
Defective response to oxidative stress characterized by elevated ROS and altered cellular metabolism
142:(difficulty with control of movement) that is apparent early but worsens in school to pre-teen years
6888:
6810:
5759:
5406:
5261:
5201:
5015:
1039:
IntraBio is also conducting two parallel clinical trials with N-Acetyl-L-Leucine for the treatment
517:
432:
340:
pharynx may cause liquid, food, and saliva to be inhaled into the airway (aspiration). People with
109:
3493:"Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK"
409:
There may be difficulty in coordinating eye position and shaping the lens to see objects up close.
6483:
6358:
6125:
5929:
5914:
5902:
5652:
5603:
5440:
5303:
5191:
4768:
4706:
4688:
4670:
3256:
3167:
3011:
2727:
2684:
2632:
2548:
2497:
2190:
1981:
1664:
1487:
1395:
1068:
1056:
1044:
451:
145:
85:
5125:
3081:"DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes"
4299:
Anheim M, Tranchant C, Koenig M (February 2012). "The autosomal recessive cerebellar ataxias".
3773:
Sharma NK, Lebedeva M, Thomas T, Kovalenko OA, Stumpf JD, Shadel GS, Santos JH (January 2014).
300:
A–T can cause features of early aging such as premature graying of the hair. It can also cause
6775:
6452:
6443:
6428:
6272:
6177:
5692:
5658:
5630:
5621:
5553:
5529:
5396:
5244:
5077:
5048:
4929:
4880:
4828:
4810:
4760:
4646:
4615:"Acetyl-DL-leucine improves gait variability in patients with cerebellar ataxia-a case series"
4595:
4424:
4375:
4324:
4281:
4232:
4196:
4161:
4098:
4049:
4000:
3951:
3902:
3853:
3804:
3755:
3706:
3671:
3622:
3563:
3522:
3473:
3424:
3375:
3332:
3291:
3248:
3202:
3159:
3118:
3060:
3003:
2959:
2918:
2869:
2834:
2778:
2719:
2676:
2624:
2589:
2540:
2489:
2433:
2381:
2332:
2280:
2242:
2182:
2139:
2104:
2069:
2016:
1973:
1937:
1896:
1847:
1812:
1794:
1750:
1701:
1656:
1621:
1577:
1528:
1479:
1444:
1387:
1349:
1281:
1271:
1223:
1174:
919:
A child cannot eat enough to grow or a person of any age cannot eat enough to maintain weight;
790:
722:
654:
642:
552:
6550:
6531:
6462:
6276:
6268:
6150:
5815:
5686:
5681:
5466:
5461:
4919:
4911:
4870:
4860:
4818:
4802:
4752:
4636:
4626:
4585:
4577:
4414:
4406:
4365:
4355:
4316:
4308:
4271:
4263:
4224:
4188:
4151:
4141:
4088:
4080:
4039:
4031:
3990:
3982:
3941:
3933:
3892:
3884:
3843:
3835:
3794:
3786:
3745:
3737:
3698:
3661:
3653:
3612:
3602:
3553:
3512:
3504:
3463:
3455:
3414:
3406:
3367:
3322:
3283:
3238:
3230:
3194:
3149:
3108:
3100:
3050:
3042:
2995:
2949:
2908:
2900:
2861:
2824:
2816:
2768:
2758:
2711:
2666:
2616:
2579:
2532:
2479:
2471:
2423:
2415:
2371:
2363:
2322:
2314:
2272:
2232:
2224:
2174:
2131:
2096:
2059:
2051:
2008:
1965:
1927:
1886:
1878:
1839:
1802:
1784:
1740:
1732:
1691:
1648:
1611:
1567:
1559:
1518:
1471:
1434:
1426:
1379:
1339:
1263:
1215:
1133:
1083:
Median survival in two large cohorts studies was 25 and 19 years of age, with a wide range.
1052:
809:
4344:"Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia"
3824:"Loss of neuronal cell cycle control in ataxia–telangiectasia: a unified disease mechanism"
3642:"ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair"
1546:
Asadollahi R, Britschgi C, Joset P, Oneda B, Schindler D, Meier UR, Rauch A (August 2020).
6879:
6709:
6697:
6573:
6155:
5737:
5428:
4957:
1299:
909:
766:
661:
183:
Drooling particularly in young children when they are tired or concentrating on activities
2607:
Shiloh Y (March 2003). "ATM and related protein kinases: safeguarding genome integrity".
1684:"Current and potential therapeutic strategies for the treatment of ataxia–telangiectasia"
705:
Each of these can be distinguished from A–T by the neurologic exam and clinical history.
664:(especially IgA, IgM, IgG, and IgG subclasses) and low number of lymphocytes in the blood
4137:
4020:"EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia–telangiectasia"
3598:
3363:
3096:
2991:
2528:
2467:
2170:
1326:
Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT (November 1986).
1211:
974:
Practicing coordination (e.g. balance beam or cursive writing exercises) is not helpful.
841:
There is no treatment known to slow or stop the progression of the neurologic problems.
292:
screening tests are not helpful, but all women should have routine cancer surveillance.
236:), and various rhythmic and non-rhythmic movements with attempts at coordinated action (
6895:
6874:
6796:
6626:
6526:
6348:
6140:
5794:
5743:
5571:
5280:
5157:
4924:
4899:
4875:
4848:
4823:
4790:
4641:
4614:
4590:
4565:
4419:
4394:
4393:
Ilg W, Bastian AJ, Boesch S, Burciu RG, Celnik P, Claaßen J, et al. (April 2014).
4370:
4343:
4276:
4251:
4156:
4121:
4093:
4068:
4044:
4019:
3995:
3970:
3946:
3921:
3897:
3872:
3848:
3823:
3799:
3774:
3750:
3725:
3666:
3641:
3617:
3582:
3517:
3492:
3468:
3443:
3419:
3410:
3394:
3113:
3080:
3055:
3030:
2913:
2888:
2829:
2804:
2773:
2746:
2428:
2403:
2376:
2351:
2327:
2302:
2237:
2212:
2064:
2039:
1891:
1866:
1807:
1772:
1745:
1720:
1572:
1547:
1439:
1414:
1344:
1327:
769:
of the aprataxin gene can confirm the diagnosis. There is no enhanced risk for cancer.
708:
691:
566:
386:
203:
154:
58:
5020:
2671:
2654:
2135:
2100:
2012:
1616:
1599:
1267:
971:
Early use of computers (preschool) with word completion software should be encouraged.
6924:
6868:
6784:
5820:
5772:
5642:
5411:
5367:
5218:
4705:
for "N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)" at
3198:
2501:
1004:
570:
73:
4772:
3260:
3171:
2688:
2636:
1668:
1491:
1399:
6602:
6414:
6094:
6086:
5316:
5186:
5169:
5088:
4342:
Lefton-Greif MA, Crawford TO, McGrath-Morrow S, Carson KA, Lederman HM (May 2011).
3839:
3015:
2552:
2318:
2194:
1985:
324:
Feeding and swallowing can become difficult for people with A–T as they get older.
4701:
4683:
4665:
3920:
Li J, Chen J, Ricupero CL, Hart RP, Schwartz MS, Kusnecov A, Herrup K (May 2012).
3371:
3138:"ATM prevents the persistence and propagation of chromosome breaks in lymphocytes"
2731:
2228:
1523:
1506:
1086:
Life expectancy does not correlate well with severity of neurological impairment.
17:
5042:
4950:
4446:
4146:
3790:
3702:
2904:
2865:
2763:
2419:
2367:
2276:
6838:
5275:
5236:
5178:
5097:
5072:
4566:"Effects of acetyl-DL-leucine in patients with cerebellar ataxia: a case series"
4228:
3046:
2954:
2937:
1843:
1328:"The incidence and gene frequency of ataxia–telangiectasia in the United States"
113:
5102:
3587:
Proceedings of the National Academy of Sciences of the United States of America
3287:
3234:
3154:
3137:
6758:
6735:
6607:
6568:
5386:
5256:
5091:
5053:
5005:
4756:
4631:
4581:
4410:
4018:
Li J, Hart RP, Mallimo EM, Swerdel MR, Kusnecov AW, Herrup K (December 2013).
3986:
3888:
1789:
935:
403:
216:
186:
93:
66:
4814:
4613:
Schniepp R, Strupp M, Wuehr M, Jahn K, Dieterich M, Brandt T, Feil K (2016).
2805:"Immunoglobulin class switch recombination is impaired in Atm-deficient mice"
1798:
1010:
N-Acetyl-Leucine has been granted multiple orphan drug designations from the
915:
A feeding (gastrostomy) tube is recommended when any of the following occur:
6117:
5496:
5447:
5435:
5418:
5350:
5083:
4806:
4267:
4192:
4117:
3607:
3583:"ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS"
2475:
1219:
447:
341:
336:
332:
281:
233:
225:
175:
97:
89:
4933:
4884:
4832:
4764:
4650:
4599:
4428:
4379:
4360:
4328:
4285:
4236:
4200:
4165:
4102:
4084:
4053:
4004:
3955:
3906:
3857:
3808:
3759:
3710:
3675:
3657:
3626:
3567:
3526:
3508:
3477:
3428:
3336:
3327:
3310:
3295:
3252:
3163:
3122:
3064:
3029:
Bredemeyer AL, Huang CY, Walker LM, Bassing CH, Sleckman BP (August 2008).
3007:
2963:
2922:
2873:
2838:
2782:
2745:
Barchi M, Roig I, Di Giacomo M, de Rooij DG, Keeney S, Jasin M (May 2008).
2628:
2593:
2544:
2493:
2437:
2385:
2336:
2284:
2246:
2143:
2108:
2073:
1977:
1941:
1900:
1851:
1816:
1754:
1705:
1660:
1581:
1532:
1483:
1285:
427:
357:
Poor weight gain (during ages of expected growth) or weight loss at any age
4865:
4312:
3459:
3379:
3206:
2723:
2680:
2186:
2020:
1932:
1915:
1652:
1625:
1448:
1391:
1383:
1353:
1227:
1178:
372:
Increase in the frequency or duration of breathing or respiratory problems
6740:
6719:
6558:
6293:
5676:
5668:
5634:
5488:
5391:
5108:
3558:
3541:
2820:
2584:
2567:
2040:"Evaluation and management of pulmonary disease in ataxia–telangiectasia"
1882:
1696:
1683:
1475:
1072:
301:
285:
269:
229:
192:
168:
164:
4320:
3741:
3309:
Biton S, Dar I, Mittelman L, Pereg Y, Barzilai A, Shiloh Y (June 2006).
3104:
2999:
2536:
2715:
2055:
1736:
925:
Mealtimes are stressful or too long, interfering with other activities.
4988:
4915:
3724:
D'Souza AD, Parish IA, Krause DS, Kaech SM, Shadel GS (January 2013).
3243:
1563:
1137:
389:(prominent blood vessels) in the membrane that covers the white part (
6433:
6302:
5715:
5456:
5423:
5000:
3775:"Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia"
2484:
2449:
2447:
2178:
1365:
1363:
1248:"ATM: genome stability, neuronal development, and cancer cross paths"
813:
797:
779:
587:
including topoisomerase 1 cleavage complex (TOP1cc) dependent lesions
390:
257:
237:
221:
139:
54:
4035:
3937:
3540:
Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Yurov YB (July 2009).
2620:
908:
recommending dietary modifications, including high calorie foods or
5971:
Spinal muscular atrophy with lower extremity predominance (SMALED)
4687:
for "N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC)" at
4067:
Jiang D, Zhang Y, Hart RP, Chen J, Herrup K, Li J (December 2015).
2213:"Multiple roles of ATM in monitoring and maintaining DNA integrity"
1969:
1430:
312:
Chronic lung disease develops in more than 25% of people with A–T.
160:
Problems with infections, especially of the ears, sinuses and lungs
4395:"Consensus paper: management of degenerative cerebellar disorders"
1916:"Cancer risks and mortality in heterozygous ATM mutation carriers"
1055:
Disease) Future opportunities to develop N-Acetyl-Leucine include
878:
thrombocytopenia (ITP), several forms of arthritis, and vitiligo.
805:
753:
604:
Inappropriate cell cycle re-entry of post-mitotic (mature) neurons
580:
Failed clearance of genomically damaged neurons during development
516:
474:
426:
335:) occur, they typically present during the second decade of life.
247:
6941:
Systemic atrophies primarily affecting the central nervous system
977:
Occupational therapy is helpful for managing daily living skills.
174:
Delayed onset or incomplete pubertal development, and very early
5031:
817:
801:
79:
It prevents repair of broken DNA, increasing the risk of cancer.
6666:
6241:
6059:
6055:
5129:
366:
Foods or drinks previously enjoyed are now refused or difficult
163:
Increased incidence of cancer (primarily, but not exclusively,
1721:"Cerebral abnormalities in adults with ataxia–telangiectasia"
4669:
for "N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)" at
1719:
Lin DD, Barker PB, Lederman HM, Crawford TO (January 2014).
2568:"ATMINistrating ATM signalling: regulation of ATM by ATMIN"
2350:
Gorodetsky E, Calkins S, Ahn J, Brooks PJ (November 2007).
577:
Defective DNA damage response in neurons which can lead to
471:
How loss of the ATM protein creates a multisystem disorder
2655:"Atm-deficient mice: a paradigm of ataxia telangiectasia"
678:
particularly helpful if a child's symptoms are atypical.
551:
Approximately 95% of people with A–T have elevated serum
363:
Mealtimes longer than 40 – 45 minutes, on a regular basis
256:
Prominent blood vessels (telangiectasia) over the white (
3873:"Cytoplasmic ATM in neurons modulates synaptic function"
2032:
2030:
1165:
Boder E (1985). "Ataxia–telangiectasia: an overview".
667:
Chromosomal instability (broken pieces of chromosomes)
84:
eyes in a natural manner from one place to the next (
4978:
3871:
Li J, Han YR, Plummer MR, Herrup K (December 2009).
2404:"Mitochondrial dysfunction in ataxia–telangiectasia"
2206:
2204:
1241:
1239:
1237:
854:
aspiration into the lungs (see above sections under
69:, causing difficulty with movement and coordination.
65:
It impairs certain areas of the brain including the
6860:
6837:
6805:
6766:
6757:
6708:
6590:
6567:
6549:
6497:
6427:
6402:
6334:
6311:
6292:
6283:
6199:
6176:
6116:
6093:
5892:
5869:
5860:
5853:
5808:
5758:
5730:
5701:
5667:
5629:
5618:
5584:
5562:
5487:
5297:
5288:
5274:
5234:
5177:
5168:
5063:
4982:
4973:
Replication-Independent Double-Strand Breaks (DSBs)
3640:Cosentino C, Grieco D, Costanzo V (February 2011).
396:
Vision (ability to see objects in focus) is normal.
202:Many children are initially misdiagnosed as having
2301:Dar I, Biton S, Shiloh Y, Barzilai A (July 2006).
1593:
1591:
1192:
1190:
1188:
504:Delayed pubertal development (gonadal dysgenesis)
3971:"ATM and the epigenetics of the neuronal genome"
2648:
2646:
613:Histone hypermethylation and altered epigenetics
513:Immune system defects and immune-related cancers
224:), slower twisting movements of the upper body (
6956:DNA replication and repair-deficiency disorders
4791:"Survival probability in ataxia telangiectasia"
4784:
4782:
4516:"Search Orphan Drug Designations and Approvals"
4492:"Search Orphan Drug Designations and Approvals"
4468:"Search Orphan Drug Designations and Approvals"
3393:Lee Y, Chong MJ, McKinnon PJ (September 2001).
2258:
2256:
1682:Lavin MF, Gueven N, Bottle S, Gatti RA (2007).
4252:"Molecular pathology of ataxia telangiectasia"
2296:
2294:
6678:
6253:
6071:
5141:
2397:
2395:
8:
2936:Bagley J, Singh G, Iacomini J (April 2007).
1321:
1319:
1150:: CS1 maint: DOI inactive as of July 2024 (
820:are also targets for phosphorylation by the
180:Slowed rate of growth (weight and/or height)
4898:Yousefpour P, Chilkoti A (September 2014).
860:Symptoms: Feeding, Swallowing and Nutrition
354:Choking or coughing when eating or drinking
228:), adoption of stiff and twisted postures (
6763:
6685:
6671:
6663:
6478:Purine nucleoside phosphorylase deficiency
6326:Transient hypogammaglobulinemia of infancy
6308:
6289:
6260:
6246:
6238:
6078:
6064:
6056:
5866:
5857:
5626:
5294:
5285:
5174:
5148:
5134:
5126:
4979:
2211:Derheimer FA, Kastan MB (September 2010).
965:the point of exhaustion should be avoided.
744:Ataxia–telangiectasia like disorder (ATLD)
252:Ocular telangiectasia in a person with A–T
6819:Hereditary nonpolyposis colorectal cancer
4923:
4874:
4864:
4822:
4640:
4630:
4589:
4418:
4369:
4359:
4275:
4155:
4145:
4092:
4043:
3994:
3945:
3896:
3847:
3798:
3749:
3665:
3616:
3606:
3557:
3516:
3467:
3418:
3326:
3242:
3153:
3112:
3054:
2953:
2912:
2828:
2772:
2762:
2670:
2583:
2483:
2427:
2375:
2326:
2236:
2063:
1931:
1890:
1806:
1788:
1744:
1695:
1615:
1571:
1552:Molecular Genetics & Genomic Medicine
1522:
1438:
1343:
4539:FRANCISCO, Estela Miranda (2018-12-20).
3276:European Journal of Paediatric Neurology
1920:Journal of the National Cancer Institute
1725:AJNR. American Journal of Neuroradiology
547:Increased alpha-fetoprotein (AFP) levels
76:, causing a predisposition to infection.
4120:, McKinnon P, Desai SD (January 2011).
1956:breast cancer susceptibility alleles".
1116:
6961:Syndromes affecting the nervous system
6642:Terminal complement pathway deficiency
5937:Distal hereditary motor neuronopathies
5610:Template:Demyelinating diseases of CNS
4975:Discusses importance of the ATM kinase
1143:
4968:GeneReviews for ataxia–telangiectasia
4116:Wood LM, Sankar S, Reed RE, Haas AL,
1766:
1764:
349:Warning signs of a swallowing problem
7:
6227:Encephalocraniocutaneous lipomatosis
5788:Idiopathic intracranial hypertension
4900:"Co-opting biology to deliver drugs"
3975:Mechanisms of Ageing and Development
2809:The Journal of Experimental Medicine
1464:American Journal of Medical Genetics
837:Ataxia and other neurologic problems
660:Immunodeficiency with low levels of
657:levels in serum after 2 years of age
210:Ataxia and other neurologic problems
189:(slurred, slow, or distorted speech)
6951:IUIS-PID table 3 immunodeficiencies
6647:Paroxysmal nocturnal hemoglobinuria
4301:The New England Journal of Medicine
4250:Taylor AM, Byrd PJ (October 2005).
3315:The Journal of Biological Chemistry
2566:Kanu N, Behrens A (November 2008).
1024:U.S. Food & Drug Administration
1012:U.S. Food & Drug Administration
446:The mode of inheritance for A–T is
406:) are common, but may be treatable.
6019:Infantile progressive bulbar palsy
3411:10.1523/JNEUROSCI.21-17-06687.2001
1419:American Journal of Human Genetics
1332:American Journal of Human Genetics
479:Characteristics of the ATM protein
439:A–T is caused by mutations in the
320:Feeding, swallowing, and nutrition
232:), occasional uncontrolled jerks (
198:Premature changes in hair and skin
25:
6161:Bannayan–Riley–Ruvalcaba syndrome
5722:Template:Cerebrovascular diseases
5525:Frontotemporal lobar degeneration
4853:Orphanet Journal of Rare Diseases
4348:Orphanet Journal of Rare Diseases
4217:Molecular Genetics and Metabolism
2124:American Journal of Ophthalmology
1777:Orphanet Journal of Rare Diseases
1773:"Ataxia telangiectasia: a review"
903:Feeding, swallowing and nutrition
808:gene. This complex, known as the
119:A–T is caused by a defect in the
6931:Chromosome instability syndromes
6906:Severe combined immunodeficiency
6410:Common variable immunodeficiency
5742:For more detailed coverage, see
5720:For more detailed coverage, see
5691:For more detailed coverage, see
5657:For more detailed coverage, see
5608:For more detailed coverage, see
4904:Biotechnology and Bioengineering
4795:Archives of Disease in Childhood
2788:
773:Ataxia–oculomotor apraxia type 2
763:Ataxia–oculomotor apraxia type 1
739:Ataxia–oculomotor apraxia type 2
733:Ataxia–oculomotor apraxia type 1
607:Synaptic/vesicular dysregulation
57:refers to poor coordination and
6829:Mismatch repair cancer syndrome
6582:Idiopathic CD4+ lymphocytopenia
6207:Abdallat–Davis–Farrage syndrome
3822:Yang Y, Herrup K (March 2005).
1604:Seminars in Pediatric Neurology
653:Elevated and slowly increasing
288:, but other cancers can occur.
126:as low as 1 in 300,000 people.
6702:DNA repair-deficiency disorder
6652:Complement receptor deficiency
6522:Adenosine deaminase deficiency
3840:10.1523/JNEUROSCI.4946-04.2005
2319:10.1523/JNEUROSCI.2055-06.2006
796:The proteins expressed by the
673:Cerebellar atrophy on MRI scan
601:Defects in neuronal function:
43:ataxia–telangiectasia syndrome
27:Rare neurodegenerative disease
1:
6035:Amyotrophic lateral sclerosis
5920:Hereditary spastic paraplegia
5778:Normal pressure hydrocephalus
4256:Journal of Clinical Pathology
3372:10.1126/science.280.5366.1089
2672:10.1016/S0092-8674(00)80086-0
2229:10.1016/j.febslet.2010.05.031
2136:10.1016/s0002-9394(02)01796-8
2101:10.1016/s0022-3476(00)70106-5
2013:10.1016/s0022-3476(05)83043-4
1617:10.1016/s1071-9091(98)80007-7
1598:Crawford TO (December 1998).
1524:10.1136/jmedgenet-2018-105635
1268:10.1016/s0065-230x(01)83007-4
1061:Amyotrophic lateral sclerosis
6780:DeSanctis–Cacchione syndrome
6726:Aicardi–Goutières syndrome 4
6004:Progressive muscular atrophy
4147:10.1371/journal.pone.0016422
3791:10.1016/j.dnarep.2013.11.002
3703:10.1016/j.dnarep.2008.03.006
3199:10.1016/0014-4827(82)90169-0
2905:10.1016/j.molcel.2009.04.025
2866:10.1016/j.dnarep.2006.05.024
2764:10.1371/journal.pgen.1000076
2420:10.1182/blood-2011-08-373639
2368:10.1016/j.dnarep.2007.06.011
2277:10.1016/j.dnarep.2004.03.029
1246:Shiloh Y, Kastan MB (2001).
6946:Neurodegenerative disorders
6321:X-linked agammaglobulinemia
6146:Multiple hamartoma syndrome
5514:Primary progressive aphasia
4229:10.1016/j.ymgme.2003.09.008
3828:The Journal of Neuroscience
3399:The Journal of Neuroscience
3047:10.4049/jimmunol.181.4.2620
2955:10.4049/jimmunol.178.8.4757
2307:The Journal of Neuroscience
1844:10.1016/j.jpeds.2003.12.046
1511:Journal of Medical Genetics
1252:Advances in Cancer Research
1041:Niemann-Pick disease type C
930:Education and socialization
491:Cancer and radiosensitivity
375:Increase in lung infections
53:causing severe disability.
6987:
6852:Nijmegen breakage syndrome
6768:Nucleotide excision repair
5836:Hashimoto's encephalopathy
5542:Posterior cortical atrophy
5363:Striatonigral degeneration
5214:Cavernous sinus thrombosis
3288:10.1016/j.ejpn.2007.04.001
3235:10.1016/j.cell.2009.03.037
3187:Experimental Cell Research
3155:10.1016/j.cell.2007.06.016
922:Aspiration is problematic;
787:Nijmegen breakage syndrome
748:Nijmegen breakage syndrome
741:(AOA2 also known as SCAR1)
6885:Rothmund–Thomson syndrome
6108:Von Hippel–Lindau disease
5942:Spinal muscular atrophies
5910:Primary lateral sclerosis
5768:Intracranial hypertension
5548:Creutzfeldt–Jakob disease
4757:10.1007/s00415-018-9155-6
4632:10.1186/s40673-016-0046-2
4582:10.1007/s00415-013-7016-x
4545:European Medicines Agency
4411:10.1007/s12311-013-0531-6
4181:The Journal of Pediatrics
3987:10.1016/j.mad.2013.05.005
3969:Herrup K (October 2013).
3889:10.1016/j.cub.2009.10.039
2089:The Journal of Pediatrics
2001:The Journal of Pediatrics
1871:British Journal of Cancer
1832:The Journal of Pediatrics
1790:10.1186/s13023-016-0543-7
1028:European Medicines Agency
1016:European Medicines Agency
598:Mitochondrial dysfunction
583:Transcription stress and
569:and, to a lesser extent,
521:ATM and the immune system
51:neurodegenerative disease
6537:Bare lymphocyte syndrome
6389:Wiskott–Aldrich syndrome
6166:Lhermitte–Duclos disease
6009:Progressive bulbar palsy
5800:Intracranial hypotension
5783:Choroid plexus papilloma
5197:Herpesviral encephalitis
4951:About A–T from the NINDS
4619:Cerebellum & Ataxias
3546:Human Molecular Genetics
1688:British Medical Bulletin
800:(defective in ATLD) and
701:Cogan oculomotor apraxia
618:Altered protein turnover
331:If swallowing problems (
6717:Separation/initiation:
6637:Complement 3 deficiency
6622:Complement 4 deficiency
6618:Complement 2 deficiency
6135:Pallister–Hall syndrome
5521:Frontotemporal dementia
5207:Encephalitis lethargica
4807:10.1136/adc.2006.094268
4268:10.1136/jcp.2005.026062
4193:10.1067/mpd.2002.123879
3608:10.1073/pnas.0913860107
2476:10.1126/science.1192912
1600:"Ataxia telangiectasia"
1304:Genetics Home Reference
1300:"Ataxia–telangiectasia"
1220:10.1126/science.7792600
1104:Phase II clinical trial
1020:Spinocerebellar Ataxias
946:General recommendations
431:A–T is inherited in an
195:in adolescence or later
41:), also referred to as
6747:Dyskeratosis congenita
6222:Peutz–Jeghers syndrome
6217:Incontinentia pigmenti
6131:Hypothalamic hamartoma
5826:Hepatic encephalopathy
4789:Crawford, T O (2005).
4699:Clinical trial number
4681:Clinical trial number
4663:Clinical trial number
4520:www.accessdata.fda.gov
4496:www.accessdata.fda.gov
4472:www.accessdata.fda.gov
4361:10.1186/1750-1172-6-23
3658:10.1038/emboj.2010.330
3509:10.1038/emboj.2009.302
3328:10.1074/jbc.M601895200
2609:Nature Reviews. Cancer
1167:Kroc Foundation Series
1140:(inactive 2024-07-15).
856:Symptoms: Lung Disease
759:
682:Differential diagnosis
585:abortive transcription
522:
480:
436:
253:
6966:Syndromes with tumors
6847:Ataxia–telangiectasia
6790:Xeroderma pigmentosum
6612:Hereditary angioedema
6468:Ataxia–telangiectasia
6313:Hypogammaglobulinemia
6212:Ataxia telangiectasia
6103:Sturge–Weber syndrome
5884:Ataxia–telangiectasia
5841:Static encephalopathy
5564:Mitochondrial disease
5402:Spasmodic torticollis
5312:Basal ganglia disease
5103:Ataxia-telangiectasia
4866:10.1186/1750-1172-9-5
4313:10.1056/NEJMra1006610
3460:10.1038/embor.2009.97
3035:Journal of Immunology
2942:Journal of Immunology
2044:Pediatric Pulmonology
1653:10.1212/wnl.54.7.1505
1384:10.1542/peds.102.1.98
1065:Restless Leg Syndrome
757:
520:
478:
430:
251:
151:Involuntary movements
31:Ataxia–telangiectasia
6901:Li–Fraumeni syndrome
6632:Properdin deficiency
6453:Di George's syndrome
6336:Dysgammaglobulinemia
5831:Toxic encephalopathy
5537:Lewy bodies dementia
4745:Journal of Neurology
4570:Journal of Neurology
4085:10.1093/brain/awv284
2821:10.1084/jem.20041074
2585:10.4161/cc.7.22.7044
1883:10.1038/bjc.2011.266
1476:10.1002/ajmg.a.20601
1126:Confinia Neurologica
385:Most people develop
6889:RAPADILINO syndrome
6824:Muir–Torre syndrome
6811:DNA mismatch repair
5879:Friedreich's ataxia
5262:Meningoencephalitis
5202:Limbic encephalitis
4138:2011PLoSO...616422W
4024:Nature Neuroscience
3742:10.1038/mt.2012.203
3599:2010PNAS..107.4153A
3364:1998Sci...280.1089H
3105:10.1038/nature07392
3097:2008Natur.456..819B
3000:10.1038/nature04866
2992:2006Natur.442..466B
2537:10.1038/nature01368
2529:2003Natur.421..499B
2468:2010Sci...330..517G
2171:1988Natur.336..577G
1933:10.1093/jnci/dji141
1212:1995Sci...268.1749S
1098:Research directions
697:Friedreich's ataxia
610:HDAC4 dysregulation
448:autosomal recessive
433:autosomal recessive
402:Eye misalignments (
110:autosomal recessive
6484:Hyper IgM syndrome
6394:Hyper-IgE syndrome
6359:Hyper IgM syndrome
6275:disorders causing
6126:Tuberous sclerosis
5915:Pseudobulbar palsy
5653:Status epilepticus
5604:Multiple sclerosis
5441:Myoclonic epilepsy
5304:movement disorders
5250:Acute disseminated
5192:Viral encephalitis
5064:External resources
4956:2016-12-14 at the
4707:ClinicalTrials.gov
4689:ClinicalTrials.gov
4671:ClinicalTrials.gov
4079:(Pt 12): 3520–36.
3559:10.1093/hmg/ddp207
2716:10.1038/ng1297-457
2056:10.1002/ppul.21277
1737:10.3174/ajnr.A3646
1697:10.1093/bmb/ldm012
1378:(1 Pt 1): 98–100.
1069:Multiple Sclerosis
1057:Lewy Body Dementia
1045:GM2 Gangliosidosis
760:
627:Radiation exposure
523:
481:
452:Prenatal diagnosis
437:
360:Excessive drooling
254:
146:Oculomotor apraxia
130:Symptoms and signs
86:oculomotor apraxia
47:Louis–Bar syndrome
18:Louis–Bar syndrome
6918:
6917:
6914:
6913:
6776:Cockayne syndrome
6694:Metabolic disease
6660:
6659:
6545:
6544:
6444:thymic hypoplasia
6429:T cell deficiency
6423:
6422:
6235:
6234:
6178:Neurofibromatosis
6053:
6052:
6049:
6048:
6045:
6044:
5849:
5848:
5754:
5753:
5693:Template:Headache
5659:Template:Epilepsy
5580:
5579:
5554:Vascular dementia
5397:Status dystonicus
5270:
5269:
5245:Encephalomyelitis
5123:
5122:
4916:10.1002/bit.25307
3730:Molecular Therapy
3358:(5366): 1089–91.
2860:(9–10): 1030–41.
2523:(6922): 499–506.
1690:. 81–82: 129–47.
1564:10.1002/mgg3.1409
1206:(5218): 1749–53.
1138:10.1159/000106149
723:alpha fetoprotein
719:Friedreich ataxia
655:alpha-fetoprotein
643:alpha-fetoprotein
560:Neurodegeneration
16:(Redirected from
6978:
6764:
6687:
6680:
6673:
6664:
6532:ZAP70 deficiency
6463:Nezelof syndrome
6309:
6290:
6277:immunodeficiency
6262:
6255:
6248:
6239:
6151:Proteus syndrome
6080:
6073:
6066:
6057:
5867:
5858:
5816:Brain herniation
5627:
5467:Intention tremor
5462:Essential tremor
5327:Postencephalitic
5295:
5286:
5175:
5156:Diseases of the
5150:
5143:
5136:
5127:
4980:
4963:Orphanet for A–T
4938:
4937:
4927:
4895:
4889:
4888:
4878:
4868:
4843:
4837:
4836:
4826:
4786:
4777:
4776:
4740:
4734:
4733:
4731:
4730:
4721:. Archived from
4715:
4709:
4697:
4691:
4679:
4673:
4661:
4655:
4654:
4644:
4634:
4610:
4604:
4603:
4593:
4561:
4555:
4554:
4552:
4551:
4536:
4530:
4529:
4527:
4526:
4512:
4506:
4505:
4503:
4502:
4488:
4482:
4481:
4479:
4478:
4464:
4458:
4457:
4455:
4454:
4445:. Archived from
4439:
4433:
4432:
4422:
4390:
4384:
4383:
4373:
4363:
4339:
4333:
4332:
4296:
4290:
4289:
4279:
4247:
4241:
4240:
4211:
4205:
4204:
4176:
4170:
4169:
4159:
4149:
4113:
4107:
4106:
4096:
4064:
4058:
4057:
4047:
4015:
4009:
4008:
3998:
3966:
3960:
3959:
3949:
3917:
3911:
3910:
3900:
3868:
3862:
3861:
3851:
3819:
3813:
3812:
3802:
3770:
3764:
3763:
3753:
3721:
3715:
3714:
3686:
3680:
3679:
3669:
3646:The EMBO Journal
3637:
3631:
3630:
3620:
3610:
3578:
3572:
3571:
3561:
3537:
3531:
3530:
3520:
3497:The EMBO Journal
3488:
3482:
3481:
3471:
3439:
3433:
3432:
3422:
3390:
3384:
3383:
3347:
3341:
3340:
3330:
3321:(25): 17482–91.
3306:
3300:
3299:
3271:
3265:
3264:
3246:
3217:
3211:
3210:
3182:
3176:
3175:
3157:
3133:
3127:
3126:
3116:
3091:(7223): 819–23.
3075:
3069:
3068:
3058:
3026:
3020:
3019:
2986:(7101): 466–70.
2974:
2968:
2967:
2957:
2933:
2927:
2926:
2916:
2884:
2878:
2877:
2849:
2843:
2842:
2832:
2800:
2794:
2793:
2792:
2786:
2776:
2766:
2742:
2736:
2735:
2699:
2693:
2692:
2674:
2650:
2641:
2640:
2604:
2598:
2597:
2587:
2563:
2557:
2556:
2512:
2506:
2505:
2487:
2462:(6003): 517–21.
2451:
2442:
2441:
2431:
2399:
2390:
2389:
2379:
2362:(11): 1698–707.
2347:
2341:
2340:
2330:
2298:
2289:
2288:
2271:(8–9): 889–900.
2260:
2251:
2250:
2240:
2208:
2199:
2198:
2179:10.1038/336577a0
2165:(6199): 577–80.
2154:
2148:
2147:
2119:
2113:
2112:
2084:
2078:
2077:
2067:
2034:
2025:
2024:
1996:
1990:
1989:
1952:
1946:
1945:
1935:
1911:
1905:
1904:
1894:
1862:
1856:
1855:
1827:
1821:
1820:
1810:
1792:
1768:
1759:
1758:
1748:
1716:
1710:
1709:
1699:
1679:
1673:
1672:
1636:
1630:
1629:
1619:
1595:
1586:
1585:
1575:
1543:
1537:
1536:
1526:
1502:
1496:
1495:
1459:
1453:
1452:
1442:
1410:
1404:
1403:
1367:
1358:
1357:
1347:
1323:
1314:
1313:
1311:
1310:
1296:
1290:
1289:
1243:
1232:
1231:
1194:
1183:
1182:
1162:
1156:
1155:
1149:
1141:
1121:
1005:N-Acetyl-Leucine
1000:N-Acetyl-Leucine
910:food supplements
530:Progeric changes
369:Chewing problems
21:
6986:
6985:
6981:
6980:
6979:
6977:
6976:
6975:
6921:
6920:
6919:
6910:
6880:Werner syndrome
6856:
6833:
6801:
6753:
6710:DNA replication
6704:
6698:DNA replication
6691:
6661:
6656:
6593:
6586:
6574:Lymphocytopenia
6572:
6563:
6541:
6517:
6504:
6493:
6449:hypoparathyroid
6431:
6419:
6398:
6330:
6300:
6279:
6266:
6236:
6231:
6195:
6172:
6156:Cowden syndrome
6112:
6089:
6084:
6054:
6041:
5967:Congenital DSMA
5888:
5845:
5804:
5750:
5738:Sleep disorders
5726:
5703:Cerebrovascular
5697:
5663:
5620:
5614:
5576:
5558:
5483:
5429:Choreoathetosis
5302:
5279:
5266:
5230:
5164:
5154:
5124:
5119:
5118:
5059:
5058:
4991:
4958:Wayback Machine
4947:
4942:
4941:
4910:(9): 1699–716.
4897:
4896:
4892:
4845:
4844:
4840:
4788:
4787:
4780:
4742:
4741:
4737:
4728:
4726:
4717:
4716:
4712:
4698:
4694:
4680:
4676:
4662:
4658:
4612:
4611:
4607:
4576:(10): 2556–61.
4563:
4562:
4558:
4549:
4547:
4538:
4537:
4533:
4524:
4522:
4514:
4513:
4509:
4500:
4498:
4490:
4489:
4485:
4476:
4474:
4466:
4465:
4461:
4452:
4450:
4441:
4440:
4436:
4392:
4391:
4387:
4341:
4340:
4336:
4298:
4297:
4293:
4262:(10): 1009–15.
4249:
4248:
4244:
4213:
4212:
4208:
4178:
4177:
4173:
4115:
4114:
4110:
4066:
4065:
4061:
4036:10.1038/nn.3564
4030:(12): 1745–53.
4017:
4016:
4012:
3968:
3967:
3963:
3938:10.1038/nm.2709
3926:Nature Medicine
3919:
3918:
3914:
3877:Current Biology
3870:
3869:
3865:
3821:
3820:
3816:
3772:
3771:
3767:
3723:
3722:
3718:
3688:
3687:
3683:
3639:
3638:
3634:
3580:
3579:
3575:
3552:(14): 2656–69.
3539:
3538:
3534:
3503:(23): 3667–80.
3490:
3489:
3485:
3441:
3440:
3436:
3405:(17): 6687–93.
3392:
3391:
3387:
3349:
3348:
3344:
3308:
3307:
3303:
3273:
3272:
3268:
3219:
3218:
3214:
3184:
3183:
3179:
3135:
3134:
3130:
3077:
3076:
3072:
3028:
3027:
3023:
2976:
2975:
2971:
2935:
2934:
2930:
2886:
2885:
2881:
2851:
2850:
2846:
2802:
2801:
2797:
2787:
2757:(5): e1000076.
2744:
2743:
2739:
2704:Nature Genetics
2701:
2700:
2696:
2652:
2651:
2644:
2621:10.1038/nrc1011
2606:
2605:
2601:
2565:
2564:
2560:
2514:
2513:
2509:
2453:
2452:
2445:
2414:(6): 1490–500.
2401:
2400:
2393:
2349:
2348:
2344:
2313:(29): 7767–74.
2300:
2299:
2292:
2262:
2261:
2254:
2223:(17): 3675–81.
2210:
2209:
2202:
2156:
2155:
2151:
2121:
2120:
2116:
2086:
2085:
2081:
2036:
2035:
2028:
1998:
1997:
1993:
1958:Nature Genetics
1954:
1953:
1949:
1913:
1912:
1908:
1864:
1863:
1859:
1829:
1828:
1824:
1770:
1769:
1762:
1718:
1717:
1713:
1681:
1680:
1676:
1638:
1637:
1633:
1597:
1596:
1589:
1545:
1544:
1540:
1504:
1503:
1499:
1461:
1460:
1456:
1412:
1411:
1407:
1369:
1368:
1361:
1325:
1324:
1317:
1308:
1306:
1298:
1297:
1293:
1278:
1245:
1244:
1235:
1196:
1195:
1186:
1164:
1163:
1159:
1142:
1123:
1122:
1118:
1113:
1100:
1092:
1081:
1002:
994:
948:
932:
905:
884:
847:
845:Immune problems
839:
834:
767:Genetic testing
684:
662:immunoglobulins
638:
629:
562:
549:
541:
532:
515:
506:
493:
468:
466:Pathophysiology
425:
416:
382:
322:
310:
298:
278:
270:immunoglobulins
266:
264:Immune problems
246:
234:myoclonic jerks
212:
132:
106:
72:It weakens the
28:
23:
22:
15:
12:
11:
5:
6984:
6982:
6974:
6973:
6971:Rare syndromes
6968:
6963:
6958:
6953:
6948:
6943:
6938:
6936:Genodermatoses
6933:
6923:
6922:
6916:
6915:
6912:
6911:
6909:
6908:
6903:
6898:
6896:Fanconi anemia
6893:
6892:
6891:
6882:
6877:
6875:Bloom syndrome
6864:
6862:
6858:
6857:
6855:
6854:
6849:
6843:
6841:
6835:
6834:
6832:
6831:
6826:
6821:
6815:
6813:
6803:
6802:
6800:
6799:
6797:IBIDS syndrome
6794:
6793:
6792:
6782:
6772:
6770:
6761:
6755:
6754:
6752:
6751:
6750:
6749:
6731:
6730:
6729:
6728:
6714:
6712:
6706:
6705:
6692:
6690:
6689:
6682:
6675:
6667:
6658:
6657:
6655:
6654:
6649:
6644:
6639:
6634:
6629:
6627:MBL deficiency
6624:
6615:
6598:
6596:
6588:
6587:
6585:
6584:
6578:
6576:
6565:
6564:
6562:
6561:
6555:
6553:
6547:
6546:
6543:
6542:
6540:
6539:
6534:
6529:
6527:Omenn syndrome
6524:
6508:
6506:
6495:
6494:
6492:
6491:
6472:
6471:
6465:
6456:
6439:
6437:
6425:
6424:
6421:
6420:
6418:
6417:
6412:
6406:
6404:
6400:
6399:
6397:
6396:
6391:
6386:
6380:
6375:
6370:
6365:
6356:
6354:IgM deficiency
6351:
6349:IgG deficiency
6346:
6344:IgA deficiency
6340:
6338:
6332:
6331:
6329:
6328:
6323:
6317:
6315:
6306:
6287:
6281:
6280:
6267:
6265:
6264:
6257:
6250:
6242:
6233:
6232:
6230:
6229:
6224:
6219:
6214:
6209:
6203:
6201:
6197:
6196:
6194:
6193:
6188:
6182:
6180:
6174:
6173:
6171:
6170:
6169:
6168:
6163:
6158:
6153:
6143:
6141:Megalencephaly
6138:
6128:
6122:
6120:
6114:
6113:
6111:
6110:
6105:
6099:
6097:
6091:
6090:
6085:
6083:
6082:
6075:
6068:
6060:
6051:
6050:
6047:
6046:
6043:
6042:
6040:
6039:
6038:
6037:
6026:
6025:
6024:
6023:
6022:
6021:
6016:
6006:
6001:
6000:
5999:
5994:
5989:
5988:
5987:
5982:
5977:
5969:
5964:
5959:
5954:
5949:
5939:
5925:
5924:
5923:
5922:
5917:
5912:
5898:
5896:
5890:
5889:
5887:
5886:
5881:
5875:
5873:
5864:
5855:
5851:
5850:
5847:
5846:
5844:
5843:
5838:
5833:
5828:
5823:
5818:
5812:
5810:
5806:
5805:
5803:
5802:
5797:
5795:Cerebral edema
5792:
5791:
5790:
5785:
5780:
5775:
5764:
5762:
5756:
5755:
5752:
5751:
5749:
5748:
5747:
5746:
5744:Template:Sleep
5734:
5732:
5728:
5727:
5725:
5724:
5718:
5713:
5707:
5705:
5699:
5698:
5696:
5695:
5689:
5684:
5679:
5673:
5671:
5665:
5664:
5662:
5661:
5655:
5650:
5645:
5639:
5637:
5624:
5616:
5615:
5613:
5612:
5606:
5601:
5596:
5590:
5588:
5582:
5581:
5578:
5577:
5575:
5574:
5572:Leigh syndrome
5568:
5566:
5560:
5559:
5557:
5556:
5545:
5544:
5539:
5534:
5533:
5532:
5518:
5517:
5516:
5511:
5510:
5509:
5493:
5491:
5485:
5484:
5482:
5481:
5476:
5471:
5470:
5469:
5464:
5453:
5452:
5451:
5450:
5445:
5444:
5443:
5433:
5432:
5431:
5421:
5416:
5415:
5414:
5409:
5404:
5399:
5383:
5382:
5381:
5380:
5375:
5370:
5365:
5360:
5359:
5358:
5348:
5347:
5346:
5336:
5335:
5334:
5329:
5324:
5308:
5306:
5299:Extrapyramidal
5292:
5283:
5281:encephalopathy
5272:
5271:
5268:
5267:
5265:
5264:
5259:
5254:
5253:
5252:
5241:
5239:
5232:
5231:
5229:
5228:
5227:
5226:
5216:
5211:
5210:
5209:
5204:
5199:
5194:
5183:
5181:
5172:
5166:
5165:
5158:nervous system
5155:
5153:
5152:
5145:
5138:
5130:
5121:
5120:
5117:
5116:
5105:
5094:
5080:
5068:
5067:
5065:
5061:
5060:
5057:
5056:
5045:
5034:
5023:
5008:
4992:
4987:
4986:
4984:
4983:Classification
4977:
4976:
4970:
4965:
4960:
4946:
4945:External links
4943:
4940:
4939:
4890:
4838:
4801:(7): 610–611.
4778:
4751:(2): 525–529.
4735:
4710:
4692:
4674:
4656:
4605:
4556:
4541:"EU/3/18/2059"
4531:
4507:
4483:
4459:
4434:
4385:
4334:
4291:
4242:
4206:
4171:
4108:
4059:
4010:
3961:
3912:
3883:(24): 2091–6.
3863:
3834:(10): 2522–9.
3814:
3765:
3716:
3697:(7): 1028–38.
3681:
3632:
3573:
3532:
3483:
3434:
3385:
3342:
3301:
3266:
3229:(6): 1088–99.
3212:
3177:
3128:
3070:
3021:
2969:
2948:(8): 4757–63.
2928:
2893:Molecular Cell
2879:
2844:
2815:(9): 1111–21.
2795:
2737:
2694:
2642:
2599:
2578:(22): 3483–6.
2558:
2507:
2443:
2391:
2342:
2290:
2252:
2200:
2149:
2114:
2079:
2026:
1991:
1970:10.1038/ng1837
1947:
1926:(11): 813–22.
1906:
1857:
1822:
1760:
1711:
1674:
1631:
1587:
1538:
1517:(5): 308–316.
1497:
1470:(3): 272–277.
1454:
1431:10.1086/301706
1425:(2): 334–345.
1405:
1359:
1315:
1291:
1276:
1233:
1184:
1157:
1132:(1–2): 32–42.
1115:
1114:
1112:
1109:
1107:for the drug.
1102:An open-label
1099:
1096:
1091:
1088:
1080:
1077:
1026:(FDA) and the
1014:(FDA) and the
1001:
998:
993:
990:
989:
988:
984:
981:
978:
975:
972:
969:
966:
962:
959:
955:
952:
947:
944:
931:
928:
927:
926:
923:
920:
904:
901:
883:
880:
846:
843:
838:
835:
833:
830:
752:
751:
745:
742:
736:
709:Cerebral palsy
703:
702:
699:
694:
692:Cerebral palsy
683:
680:
675:
674:
671:
668:
665:
658:
637:
634:
628:
625:
620:
619:
616:
615:
614:
611:
608:
605:
599:
596:
593:
592:
591:
588:
581:
567:Purkinje cells
561:
558:
548:
545:
540:
539:Telangiectasia
537:
531:
528:
514:
511:
505:
502:
492:
489:
467:
464:
424:
421:
415:
412:
411:
410:
407:
400:
397:
394:
387:telangiectasia
381:
380:Eye and vision
378:
377:
376:
373:
370:
367:
364:
361:
358:
355:
351:
350:
321:
318:
309:
306:
297:
294:
277:
274:
265:
262:
245:
244:Telangiectasia
242:
211:
208:
204:cerebral palsy
200:
199:
196:
190:
184:
181:
178:
172:
161:
158:
155:Telangiectasia
152:
149:
143:
131:
128:
105:
102:
81:
80:
77:
70:
59:telangiectasia
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
6983:
6972:
6969:
6967:
6964:
6962:
6959:
6957:
6954:
6952:
6949:
6947:
6944:
6942:
6939:
6937:
6934:
6932:
6929:
6928:
6926:
6907:
6904:
6902:
6899:
6897:
6894:
6890:
6886:
6883:
6881:
6878:
6876:
6873:
6872:
6871:
6870:
6869:RecQ helicase
6866:
6865:
6863:
6859:
6853:
6850:
6848:
6845:
6844:
6842:
6840:
6836:
6830:
6827:
6825:
6822:
6820:
6817:
6816:
6814:
6812:
6808:
6804:
6798:
6795:
6791:
6788:
6787:
6786:
6785:Thymine dimer
6783:
6781:
6777:
6774:
6773:
6771:
6769:
6765:
6762:
6760:
6756:
6748:
6745:
6744:
6743:
6742:
6737:
6733:
6732:
6727:
6724:
6723:
6722:
6721:
6716:
6715:
6713:
6711:
6707:
6703:
6699:
6695:
6688:
6683:
6681:
6676:
6674:
6669:
6668:
6665:
6653:
6650:
6648:
6645:
6643:
6640:
6638:
6635:
6633:
6630:
6628:
6625:
6623:
6619:
6616:
6613:
6609:
6605:
6604:
6600:
6599:
6597:
6595:
6589:
6583:
6580:
6579:
6577:
6575:
6570:
6566:
6560:
6557:
6556:
6554:
6552:
6548:
6538:
6535:
6533:
6530:
6528:
6525:
6523:
6520:
6516:
6513:
6510:
6509:
6507:
6503:
6500:
6496:
6489:
6485:
6482:
6481:
6480:
6479:
6476:
6469:
6466:
6464:
6460:
6459:euparathyroid
6457:
6454:
6450:
6447:
6445:
6441:
6440:
6438:
6435:
6430:
6426:
6416:
6413:
6411:
6408:
6407:
6405:
6401:
6395:
6392:
6390:
6387:
6384:
6381:
6379:
6376:
6374:
6371:
6369:
6366:
6364:
6360:
6357:
6355:
6352:
6350:
6347:
6345:
6342:
6341:
6339:
6337:
6333:
6327:
6324:
6322:
6319:
6318:
6316:
6314:
6310:
6307:
6304:
6299:
6295:
6291:
6288:
6286:
6282:
6278:
6274:
6270:
6263:
6258:
6256:
6251:
6249:
6244:
6243:
6240:
6228:
6225:
6223:
6220:
6218:
6215:
6213:
6210:
6208:
6205:
6204:
6202:
6198:
6192:
6189:
6187:
6184:
6183:
6181:
6179:
6175:
6167:
6164:
6162:
6159:
6157:
6154:
6152:
6149:
6148:
6147:
6144:
6142:
6139:
6136:
6132:
6129:
6127:
6124:
6123:
6121:
6119:
6115:
6109:
6106:
6104:
6101:
6100:
6098:
6096:
6092:
6088:
6081:
6076:
6074:
6069:
6067:
6062:
6061:
6058:
6036:
6033:
6032:
6031:
6028:
6027:
6020:
6017:
6015:
6012:
6011:
6010:
6007:
6005:
6002:
5998:
5995:
5993:
5990:
5986:
5983:
5981:
5978:
5976:
5973:
5972:
5970:
5968:
5965:
5963:
5960:
5958:
5955:
5953:
5950:
5948:
5945:
5944:
5943:
5940:
5938:
5935:
5934:
5933:
5931:
5927:
5926:
5921:
5918:
5916:
5913:
5911:
5908:
5907:
5906:
5904:
5900:
5899:
5897:
5895:
5891:
5885:
5882:
5880:
5877:
5876:
5874:
5872:
5868:
5865:
5863:
5859:
5856:
5852:
5842:
5839:
5837:
5834:
5832:
5829:
5827:
5824:
5822:
5821:Reye syndrome
5819:
5817:
5814:
5813:
5811:
5807:
5801:
5798:
5796:
5793:
5789:
5786:
5784:
5781:
5779:
5776:
5774:
5773:Hydrocephalus
5771:
5770:
5769:
5766:
5765:
5763:
5761:
5757:
5745:
5741:
5740:
5739:
5736:
5735:
5733:
5729:
5723:
5719:
5717:
5714:
5712:
5709:
5708:
5706:
5704:
5700:
5694:
5690:
5688:
5685:
5683:
5680:
5678:
5675:
5674:
5672:
5670:
5666:
5660:
5656:
5654:
5651:
5649:
5646:
5644:
5641:
5640:
5638:
5636:
5632:
5628:
5625:
5623:
5617:
5611:
5607:
5605:
5602:
5600:
5597:
5595:
5592:
5591:
5589:
5587:
5586:Demyelinating
5583:
5573:
5570:
5569:
5567:
5565:
5561:
5555:
5552:
5551:
5550:
5549:
5543:
5540:
5538:
5535:
5531:
5528:
5527:
5526:
5522:
5519:
5515:
5512:
5508:
5505:
5504:
5503:
5500:
5499:
5498:
5495:
5494:
5492:
5490:
5486:
5480:
5477:
5475:
5474:Restless legs
5472:
5468:
5465:
5463:
5460:
5459:
5458:
5455:
5454:
5449:
5446:
5442:
5439:
5438:
5437:
5434:
5430:
5427:
5426:
5425:
5422:
5420:
5417:
5413:
5412:Blepharospasm
5410:
5408:
5405:
5403:
5400:
5398:
5395:
5394:
5393:
5390:
5389:
5388:
5385:
5384:
5379:
5376:
5374:
5371:
5369:
5368:Hemiballismus
5366:
5364:
5361:
5357:
5354:
5353:
5352:
5349:
5345:
5342:
5341:
5340:
5337:
5333:
5330:
5328:
5325:
5323:
5320:
5319:
5318:
5315:
5314:
5313:
5310:
5309:
5307:
5305:
5300:
5296:
5293:
5291:
5287:
5284:
5282:
5277:
5273:
5263:
5260:
5258:
5255:
5251:
5248:
5247:
5246:
5243:
5242:
5240:
5238:
5233:
5225:
5222:
5221:
5220:
5219:Brain abscess
5217:
5215:
5212:
5208:
5205:
5203:
5200:
5198:
5195:
5193:
5190:
5189:
5188:
5185:
5184:
5182:
5180:
5176:
5173:
5171:
5167:
5163:
5159:
5151:
5146:
5144:
5139:
5137:
5132:
5131:
5128:
5115:
5111:
5110:
5106:
5104:
5100:
5099:
5095:
5093:
5090:
5086:
5085:
5081:
5079:
5075:
5074:
5070:
5069:
5066:
5062:
5055:
5051:
5050:
5046:
5044:
5040:
5039:
5035:
5033:
5029:
5028:
5024:
5022:
5018:
5017:
5013:
5009:
5007:
5003:
5002:
4998:
4994:
4993:
4990:
4985:
4981:
4974:
4971:
4969:
4966:
4964:
4961:
4959:
4955:
4952:
4949:
4948:
4944:
4935:
4931:
4926:
4921:
4917:
4913:
4909:
4905:
4901:
4894:
4891:
4886:
4882:
4877:
4872:
4867:
4862:
4858:
4854:
4850:
4842:
4839:
4834:
4830:
4825:
4820:
4816:
4812:
4808:
4804:
4800:
4796:
4792:
4785:
4783:
4779:
4774:
4770:
4766:
4762:
4758:
4754:
4750:
4746:
4739:
4736:
4725:on 2019-08-01
4724:
4720:
4714:
4711:
4708:
4704:
4703:
4696:
4693:
4690:
4686:
4685:
4678:
4675:
4672:
4668:
4667:
4660:
4657:
4652:
4648:
4643:
4638:
4633:
4628:
4624:
4620:
4616:
4609:
4606:
4601:
4597:
4592:
4587:
4583:
4579:
4575:
4571:
4567:
4560:
4557:
4546:
4542:
4535:
4532:
4521:
4517:
4511:
4508:
4497:
4493:
4487:
4484:
4473:
4469:
4463:
4460:
4449:on 2019-08-01
4448:
4444:
4438:
4435:
4430:
4426:
4421:
4416:
4412:
4408:
4405:(2): 248–68.
4404:
4400:
4396:
4389:
4386:
4381:
4377:
4372:
4367:
4362:
4357:
4353:
4349:
4345:
4338:
4335:
4330:
4326:
4322:
4318:
4314:
4310:
4307:(7): 636–46.
4306:
4302:
4295:
4292:
4287:
4283:
4278:
4273:
4269:
4265:
4261:
4257:
4253:
4246:
4243:
4238:
4234:
4230:
4226:
4223:(4): 437–43.
4222:
4218:
4210:
4207:
4202:
4198:
4194:
4190:
4187:(6): 724–31.
4186:
4182:
4175:
4172:
4167:
4163:
4158:
4153:
4148:
4143:
4139:
4135:
4132:(1): e16422.
4131:
4127:
4123:
4119:
4112:
4109:
4104:
4100:
4095:
4090:
4086:
4082:
4078:
4074:
4070:
4063:
4060:
4055:
4051:
4046:
4041:
4037:
4033:
4029:
4025:
4021:
4014:
4011:
4006:
4002:
3997:
3992:
3988:
3984:
3981:(10): 434–9.
3980:
3976:
3972:
3965:
3962:
3957:
3953:
3948:
3943:
3939:
3935:
3932:(5): 783–90.
3931:
3927:
3923:
3916:
3913:
3908:
3904:
3899:
3894:
3890:
3886:
3882:
3878:
3874:
3867:
3864:
3859:
3855:
3850:
3845:
3841:
3837:
3833:
3829:
3825:
3818:
3815:
3810:
3806:
3801:
3796:
3792:
3788:
3784:
3780:
3776:
3769:
3766:
3761:
3757:
3752:
3747:
3743:
3739:
3735:
3731:
3727:
3720:
3717:
3712:
3708:
3704:
3700:
3696:
3692:
3685:
3682:
3677:
3673:
3668:
3663:
3659:
3655:
3652:(3): 546–55.
3651:
3647:
3643:
3636:
3633:
3628:
3624:
3619:
3614:
3609:
3604:
3600:
3596:
3593:(9): 4153–8.
3592:
3588:
3584:
3577:
3574:
3569:
3565:
3560:
3555:
3551:
3547:
3543:
3536:
3533:
3528:
3524:
3519:
3514:
3510:
3506:
3502:
3498:
3494:
3487:
3484:
3479:
3475:
3470:
3465:
3461:
3457:
3454:(8): 887–93.
3453:
3449:
3445:
3438:
3435:
3430:
3426:
3421:
3416:
3412:
3408:
3404:
3400:
3396:
3389:
3386:
3381:
3377:
3373:
3369:
3365:
3361:
3357:
3353:
3346:
3343:
3338:
3334:
3329:
3324:
3320:
3316:
3312:
3305:
3302:
3297:
3293:
3289:
3285:
3282:(6): 375–80.
3281:
3277:
3270:
3267:
3262:
3258:
3254:
3250:
3245:
3240:
3236:
3232:
3228:
3224:
3216:
3213:
3208:
3204:
3200:
3196:
3192:
3188:
3181:
3178:
3173:
3169:
3165:
3161:
3156:
3151:
3147:
3143:
3139:
3132:
3129:
3124:
3120:
3115:
3110:
3106:
3102:
3098:
3094:
3090:
3086:
3082:
3074:
3071:
3066:
3062:
3057:
3052:
3048:
3044:
3041:(4): 2620–5.
3040:
3036:
3032:
3025:
3022:
3017:
3013:
3009:
3005:
3001:
2997:
2993:
2989:
2985:
2981:
2973:
2970:
2965:
2961:
2956:
2951:
2947:
2943:
2939:
2932:
2929:
2924:
2920:
2915:
2910:
2906:
2902:
2899:(3): 285–97.
2898:
2894:
2890:
2883:
2880:
2875:
2871:
2867:
2863:
2859:
2855:
2848:
2845:
2840:
2836:
2831:
2826:
2822:
2818:
2814:
2810:
2806:
2799:
2796:
2791:
2784:
2780:
2775:
2770:
2765:
2760:
2756:
2752:
2751:PLOS Genetics
2748:
2741:
2738:
2733:
2729:
2725:
2721:
2717:
2713:
2710:(4): 457–61.
2709:
2705:
2698:
2695:
2690:
2686:
2682:
2678:
2673:
2668:
2665:(1): 159–71.
2664:
2660:
2656:
2649:
2647:
2643:
2638:
2634:
2630:
2626:
2622:
2618:
2615:(3): 155–68.
2614:
2610:
2603:
2600:
2595:
2591:
2586:
2581:
2577:
2573:
2569:
2562:
2559:
2554:
2550:
2546:
2542:
2538:
2534:
2530:
2526:
2522:
2518:
2511:
2508:
2503:
2499:
2495:
2491:
2486:
2481:
2477:
2473:
2469:
2465:
2461:
2457:
2450:
2448:
2444:
2439:
2435:
2430:
2425:
2421:
2417:
2413:
2409:
2405:
2398:
2396:
2392:
2387:
2383:
2378:
2373:
2369:
2365:
2361:
2357:
2353:
2346:
2343:
2338:
2334:
2329:
2324:
2320:
2316:
2312:
2308:
2304:
2297:
2295:
2291:
2286:
2282:
2278:
2274:
2270:
2266:
2259:
2257:
2253:
2248:
2244:
2239:
2234:
2230:
2226:
2222:
2218:
2214:
2207:
2205:
2201:
2196:
2192:
2188:
2184:
2180:
2176:
2172:
2168:
2164:
2160:
2153:
2150:
2145:
2141:
2137:
2133:
2129:
2125:
2118:
2115:
2110:
2106:
2102:
2098:
2095:(2): 225–31.
2094:
2090:
2083:
2080:
2075:
2071:
2066:
2061:
2057:
2053:
2050:(9): 847–59.
2049:
2045:
2041:
2033:
2031:
2027:
2022:
2018:
2014:
2010:
2007:(6): 917–22.
2006:
2002:
1995:
1992:
1987:
1983:
1979:
1975:
1971:
1967:
1963:
1959:
1951:
1948:
1943:
1939:
1934:
1929:
1925:
1921:
1917:
1910:
1907:
1902:
1898:
1893:
1888:
1884:
1880:
1877:(4): 586–91.
1876:
1872:
1868:
1861:
1858:
1853:
1849:
1845:
1841:
1838:(4): 505–11.
1837:
1833:
1826:
1823:
1818:
1814:
1809:
1804:
1800:
1796:
1791:
1786:
1782:
1778:
1774:
1767:
1765:
1761:
1756:
1752:
1747:
1742:
1738:
1734:
1731:(1): 119–23.
1730:
1726:
1722:
1715:
1712:
1707:
1703:
1698:
1693:
1689:
1685:
1678:
1675:
1670:
1666:
1662:
1658:
1654:
1650:
1647:(7): 1505–9.
1646:
1642:
1635:
1632:
1627:
1623:
1618:
1613:
1610:(4): 287–94.
1609:
1605:
1601:
1594:
1592:
1588:
1583:
1579:
1574:
1569:
1565:
1561:
1558:(10): e1409.
1557:
1553:
1549:
1542:
1539:
1534:
1530:
1525:
1520:
1516:
1512:
1508:
1501:
1498:
1493:
1489:
1485:
1481:
1477:
1473:
1469:
1465:
1458:
1455:
1450:
1446:
1441:
1436:
1432:
1428:
1424:
1420:
1416:
1409:
1406:
1401:
1397:
1393:
1389:
1385:
1381:
1377:
1373:
1366:
1364:
1360:
1355:
1351:
1346:
1341:
1338:(5): 573–83.
1337:
1333:
1329:
1322:
1320:
1316:
1305:
1301:
1295:
1292:
1287:
1283:
1279:
1277:9780120066834
1273:
1269:
1265:
1261:
1257:
1253:
1249:
1242:
1240:
1238:
1234:
1229:
1225:
1221:
1217:
1213:
1209:
1205:
1201:
1193:
1191:
1189:
1185:
1180:
1176:
1172:
1168:
1161:
1158:
1153:
1147:
1139:
1135:
1131:
1127:
1120:
1117:
1110:
1108:
1105:
1097:
1095:
1089:
1087:
1084:
1078:
1076:
1074:
1070:
1066:
1062:
1058:
1054:
1050:
1046:
1042:
1037:
1034:
1031:
1029:
1025:
1021:
1017:
1013:
1008:
1006:
999:
997:
991:
985:
982:
979:
976:
973:
970:
967:
963:
960:
956:
953:
950:
949:
945:
943:
939:
937:
929:
924:
921:
918:
917:
916:
913:
911:
902:
900:
896:
892:
891:antibiotics.
888:
881:
879:
875:
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867:
863:
861:
857:
851:
844:
842:
836:
831:
829:
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823:
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807:
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784:
781:
776:
774:
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764:
756:
749:
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734:
731:
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603:
602:
600:
597:
594:
589:
586:
582:
579:
578:
576:
575:
574:
572:
571:granule cells
568:
559:
557:
554:
546:
544:
538:
536:
529:
527:
519:
512:
510:
503:
501:
497:
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477:
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465:
463:
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455:
453:
449:
444:
442:
434:
429:
422:
420:
413:
408:
405:
401:
398:
395:
393:) of the eye.
392:
388:
384:
383:
379:
374:
371:
368:
365:
362:
359:
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353:
352:
348:
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319:
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295:
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129:
127:
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117:
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111:
103:
101:
99:
95:
91:
87:
78:
75:
74:immune system
71:
68:
64:
63:
62:
60:
56:
52:
49:, is a rare,
48:
44:
40:
36:
32:
19:
6867:
6846:
6739:
6734:Termination/
6718:
6603:C1-inhibitor
6601:
6518:
6511:
6474:
6473:
6467:
6458:
6448:
6442:
6415:ICF syndrome
6095:Angiomatosis
6087:Phakomatosis
6029:
5928:
5901:
5883:
5862:Degenerative
5599:Inflammatory
5546:
5479:Stiff-person
5317:Parkinsonism
5290:Degenerative
5187:Encephalitis
5170:Inflammation
5160:, primarily
5107:
5096:
5082:
5071:
5047:
5036:
5025:
5010:
4995:
4907:
4903:
4893:
4856:
4852:
4841:
4798:
4794:
4748:
4744:
4738:
4727:. Retrieved
4723:the original
4713:
4700:
4695:
4682:
4677:
4664:
4659:
4622:
4618:
4608:
4573:
4569:
4559:
4548:. Retrieved
4544:
4534:
4523:. Retrieved
4519:
4510:
4499:. Retrieved
4495:
4486:
4475:. Retrieved
4471:
4462:
4451:. Retrieved
4447:the original
4437:
4402:
4398:
4388:
4351:
4347:
4337:
4321:10068/785252
4304:
4300:
4294:
4259:
4255:
4245:
4220:
4216:
4209:
4184:
4180:
4174:
4129:
4125:
4111:
4076:
4072:
4062:
4027:
4023:
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3978:
3974:
3964:
3929:
3925:
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3880:
3876:
3866:
3831:
3827:
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3778:
3768:
3733:
3729:
3719:
3694:
3690:
3684:
3649:
3645:
3635:
3590:
3586:
3576:
3549:
3545:
3535:
3500:
3496:
3486:
3451:
3448:EMBO Reports
3447:
3437:
3402:
3398:
3388:
3355:
3351:
3345:
3318:
3314:
3304:
3279:
3275:
3269:
3226:
3222:
3215:
3193:(1): 191–9.
3190:
3186:
3180:
3148:(1): 63–75.
3145:
3141:
3131:
3088:
3084:
3073:
3038:
3034:
3024:
2983:
2979:
2972:
2945:
2941:
2931:
2896:
2892:
2882:
2857:
2853:
2847:
2812:
2808:
2798:
2754:
2750:
2740:
2707:
2703:
2697:
2662:
2658:
2612:
2608:
2602:
2575:
2571:
2561:
2520:
2516:
2510:
2459:
2455:
2411:
2407:
2359:
2355:
2345:
2310:
2306:
2268:
2264:
2220:
2217:FEBS Letters
2216:
2162:
2158:
2152:
2130:(6): 891–6.
2127:
2123:
2117:
2092:
2088:
2082:
2047:
2043:
2004:
2000:
1994:
1964:(8): 873–5.
1961:
1957:
1950:
1923:
1919:
1909:
1874:
1870:
1860:
1835:
1831:
1825:
1780:
1776:
1728:
1724:
1714:
1687:
1677:
1644:
1640:
1634:
1607:
1603:
1555:
1551:
1541:
1514:
1510:
1500:
1467:
1463:
1457:
1422:
1418:
1408:
1375:
1371:
1335:
1331:
1307:. Retrieved
1303:
1294:
1255:
1251:
1203:
1199:
1170:
1166:
1160:
1146:cite journal
1129:
1125:
1119:
1101:
1093:
1090:Epidemiology
1085:
1082:
1038:
1035:
1032:
1009:
1003:
995:
940:
933:
914:
906:
897:
893:
889:
885:
882:Lung disease
876:
872:
868:
864:
859:
855:
852:
848:
840:
826:
795:
785:
777:
771:
761:
727:
717:
713:
707:
704:
685:
676:
647:
639:
630:
621:
563:
550:
542:
533:
524:
507:
498:
494:
484:
482:
470:
469:
460:
456:
445:
438:
417:
330:
326:
323:
314:
311:
308:Lung disease
299:
290:
279:
267:
255:
213:
201:
133:
121:
118:
107:
82:
46:
42:
38:
34:
30:
29:
6839:MRN complex
6475:peripheral:
6014:Fazio–Londe
5854:Both/either
5648:Generalised
5507:Early-onset
5502:Alzheimer's
5237:spinal cord
5098:GeneReviews
5073:MedlinePlus
4702:NCT03759665
4684:NCT03759639
4666:NCT03759678
3736:(1): 42–8.
414:Orthopedics
114:inheritance
112:pattern of
108:A–T has an
6925:Categories
6759:DNA repair
6736:telomerase
6608:Angioedema
6594:deficiency
6592:Complement
6569:Leukopenia
6519:autosomal:
6273:complement
5622:paroxysmal
5594:Autoimmune
5387:Dyskinesia
5257:Meningitis
5235:Brain and
5049:DiseasesDB
4729:2019-08-01
4719:"IntraBio"
4550:2019-08-01
4525:2019-08-01
4501:2019-08-01
4477:2019-08-01
4453:2019-08-01
4443:"IntraBio"
4399:Cerebellum
3779:DNA Repair
3691:DNA Repair
3244:2297/19337
2854:DNA Repair
2572:Cell Cycle
2356:DNA Repair
2265:DNA Repair
1783:(1): 159.
1372:Pediatrics
1309:2018-03-29
1111:References
936:dysarthria
832:Management
590:Aneuploidy
404:strabismus
217:wheelchair
187:Dysarthria
94:bronchitis
67:cerebellum
6512:x-linked:
6118:Hamartoma
5619:Episodic/
5497:Tauopathy
5448:Akathisia
5436:Myoclonus
5419:Athetosis
5351:Tauopathy
5084:eMedicine
4815:0003-9888
3785:: 22–31.
2502:206527888
2485:2152/9689
1799:1750-1172
1641:Neurology
1079:Prognosis
1049:Tay-Sachs
992:Treatment
636:Diagnosis
342:dysphagia
337:Dysphagia
333:dysphagia
282:lymphomas
226:athetosis
176:menopause
169:leukemias
165:lymphomas
98:pneumonia
90:sinusitis
6720:RNASEH2A
6559:HIV/AIDS
6551:Acquired
6502:combined
6294:Antibody
6269:Lymphoid
5985:SMALED2B
5980:SMALED2A
5677:Migraine
5669:Headache
5635:epilepsy
5631:Seizures
5489:Dementia
5392:Dystonia
5109:Orphanet
5089:derm/691
4954:Archived
4934:24916780
4885:24405665
4859:(1): 5.
4833:16790721
4773:56148131
4765:30547273
4651:27073690
4600:23835634
4429:24222635
4380:21569628
4329:22335741
4286:16189143
4237:14654357
4201:12072877
4166:21298066
4126:PLOS ONE
4103:26510954
4054:24162653
4005:23707635
3956:22466704
3907:19962314
3858:15758161
3809:24342190
3760:23011031
3711:18456574
3676:21157431
3627:20160076
3568:19414482
3527:19851285
3478:19557000
3429:11517258
3337:16627474
3296:17540590
3261:16630060
3253:19524511
3172:17514413
3164:17599403
3123:18849970
3065:18684952
3008:16799570
2964:17404255
2923:19450527
2874:16934538
2839:15504820
2783:18497861
2689:11922073
2637:22770833
2629:12612651
2594:19001856
2545:12556884
2494:20966255
2438:22144182
2386:17706468
2337:16855104
2285:15279774
2247:20580718
2144:12470759
2109:10657830
2074:20583220
1978:16832357
1942:15928302
1901:21792198
1852:15069401
1817:27884168
1755:23886747
1706:17586848
1669:24908122
1661:10751267
1582:32748564
1533:30819809
1492:22090621
1484:15054841
1400:22538515
1286:11665719
1173:: 1–63.
1073:Migraine
1053:Sandhoff
987:helpful.
423:Genetics
302:vitiligo
286:leukemia
230:dystonia
193:Diabetes
6298:humoral
6285:Primary
6191:Type II
5997:SMA-PME
5992:SMA-PCH
5975:SMALED1
5687:Tension
5682:Cluster
5407:Meige's
5224:Amoebic
5092:oph/319
5043:D001260
4925:4251460
4876:3904207
4824:2082822
4642:4828858
4591:3824630
4420:4344126
4371:3116459
4277:1770730
4157:3027683
4134:Bibcode
4094:4668921
4045:3965909
3996:3791148
3947:3378917
3898:2805770
3849:6725172
3800:6211587
3751:3538311
3667:3034007
3618:2840158
3595:Bibcode
3518:2790489
3469:2726680
3420:6763074
3380:9582124
3360:Bibcode
3352:Science
3207:6213420
3114:2605662
3093:Bibcode
3056:3598579
3016:4320129
2988:Bibcode
2914:2709792
2830:2211853
2774:2374915
2724:9398850
2681:8689683
2553:4403303
2525:Bibcode
2464:Bibcode
2456:Science
2429:3286212
2377:2797317
2328:6674276
2238:2950315
2195:4255660
2187:3200306
2167:Bibcode
2065:4151879
2021:1960607
1986:2909283
1892:3170966
1808:5123280
1746:4106125
1626:9874856
1573:7549565
1449:9463314
1440:1376883
1392:9651420
1354:3788973
1345:1684065
1228:7792600
1208:Bibcode
1200:Science
1179:2415689
1030:(EMA).
435:fashion
238:tremors
6515:X-SCID
6499:Severe
6186:Type I
5716:Stroke
5530:Pick's
5457:Tremor
5424:Chorea
5078:001394
5032:208900
4932:
4922:
4883:
4873:
4831:
4821:
4813:
4771:
4763:
4649:
4639:
4598:
4588:
4427:
4417:
4378:
4368:
4354:: 23.
4327:
4284:
4274:
4235:
4199:
4164:
4154:
4118:Liu LF
4101:
4091:
4052:
4042:
4003:
3993:
3954:
3944:
3905:
3895:
3856:
3846:
3807:
3797:
3758:
3748:
3709:
3674:
3664:
3625:
3615:
3566:
3525:
3515:
3476:
3466:
3427:
3417:
3378:
3335:
3294:
3259:
3251:
3205:
3170:
3162:
3121:
3111:
3085:Nature
3063:
3053:
3014:
3006:
2980:Nature
2962:
2921:
2911:
2872:
2837:
2827:
2781:
2771:
2732:193465
2730:
2722:
2687:
2679:
2635:
2627:
2592:
2551:
2543:
2517:Nature
2500:
2492:
2436:
2426:
2384:
2374:
2335:
2325:
2283:
2245:
2235:
2193:
2185:
2159:Nature
2142:
2107:
2072:
2062:
2019:
1984:
1976:
1940:
1899:
1889:
1850:
1815:
1805:
1797:
1753:
1743:
1704:
1667:
1659:
1624:
1580:
1570:
1531:
1490:
1482:
1447:
1437:
1398:
1390:
1352:
1342:
1284:
1274:
1260:209–54
1226:
1177:
1071:, and
806:hRad50
798:hMre11
780:hMre11
735:(AOA1)
391:sclera
276:Cancer
258:sclera
222:chorea
140:Ataxia
104:Causes
96:, and
55:Ataxia
6861:Other
6505:(B+T)
6403:Other
6200:Other
6030:both:
5962:DSMA1
5957:SMAX2
5952:SMAX1
5932:only:
5905:only:
5809:Other
5731:Other
5643:Focal
5276:Brain
5179:Brain
5021:334.8
5006:G11.3
4769:S2CID
4625:: 8.
4073:Brain
3257:S2CID
3168:S2CID
3012:S2CID
2728:S2CID
2685:S2CID
2633:S2CID
2549:S2CID
2498:S2CID
2408:Blood
2191:S2CID
1982:S2CID
1665:S2CID
1488:S2CID
1396:S2CID
814:Mre11
750:(NBS)
6741:DKC1
6700:and
6271:and
5633:and
5344:PKAN
5339:NBIA
5054:1025
5038:MeSH
5027:OMIM
5016:9-CM
4930:PMID
4881:PMID
4829:PMID
4811:ISSN
4761:PMID
4647:PMID
4596:PMID
4425:PMID
4376:PMID
4325:PMID
4282:PMID
4233:PMID
4197:PMID
4162:PMID
4099:PMID
4050:PMID
4001:PMID
3952:PMID
3903:PMID
3854:PMID
3805:PMID
3756:PMID
3707:PMID
3672:PMID
3623:PMID
3564:PMID
3523:PMID
3474:PMID
3425:PMID
3376:PMID
3333:PMID
3292:PMID
3249:PMID
3223:Cell
3203:PMID
3160:PMID
3142:Cell
3119:PMID
3061:PMID
3004:PMID
2960:PMID
2919:PMID
2870:PMID
2835:PMID
2779:PMID
2720:PMID
2677:PMID
2659:Cell
2625:PMID
2590:PMID
2541:PMID
2490:PMID
2434:PMID
2382:PMID
2333:PMID
2281:PMID
2243:PMID
2183:PMID
2140:PMID
2105:PMID
2070:PMID
2017:PMID
1974:PMID
1938:PMID
1897:PMID
1848:PMID
1813:PMID
1795:ISSN
1751:PMID
1702:PMID
1657:PMID
1622:PMID
1578:PMID
1529:PMID
1480:PMID
1468:126A
1445:PMID
1388:PMID
1350:PMID
1282:PMID
1272:ISBN
1224:PMID
1175:PMID
1152:link
1051:and
1043:and
858:and
818:Nbs1
816:and
802:Nbs1
296:Skin
284:and
167:and
6807:MSI
5947:SMA
5930:LMN
5903:UMN
5894:MND
5760:CSF
5711:TIA
5356:PSP
5332:NMS
5301:and
5162:CNS
5114:100
5012:ICD
4997:ICD
4920:PMC
4912:doi
4908:111
4871:PMC
4861:doi
4819:PMC
4803:doi
4753:doi
4749:266
4637:PMC
4627:doi
4586:PMC
4578:doi
4574:260
4415:PMC
4407:doi
4366:PMC
4356:doi
4317:hdl
4309:doi
4305:366
4272:PMC
4264:doi
4225:doi
4189:doi
4185:140
4152:PMC
4142:doi
4089:PMC
4081:doi
4077:138
4040:PMC
4032:doi
3991:PMC
3983:doi
3979:134
3942:PMC
3934:doi
3893:PMC
3885:doi
3844:PMC
3836:doi
3795:PMC
3787:doi
3746:PMC
3738:doi
3699:doi
3662:PMC
3654:doi
3613:PMC
3603:doi
3591:107
3554:doi
3513:PMC
3505:doi
3464:PMC
3456:doi
3415:PMC
3407:doi
3368:doi
3356:280
3323:doi
3319:281
3284:doi
3239:hdl
3231:doi
3227:137
3195:doi
3191:140
3150:doi
3146:130
3109:PMC
3101:doi
3089:456
3051:PMC
3043:doi
3039:181
2996:doi
2984:442
2950:doi
2946:178
2909:PMC
2901:doi
2862:doi
2825:PMC
2817:doi
2813:200
2769:PMC
2759:doi
2712:doi
2667:doi
2617:doi
2580:doi
2533:doi
2521:421
2480:hdl
2472:doi
2460:330
2424:PMC
2416:doi
2412:119
2372:PMC
2364:doi
2323:PMC
2315:doi
2273:doi
2233:PMC
2225:doi
2221:584
2175:doi
2163:336
2132:doi
2128:134
2097:doi
2093:136
2060:PMC
2052:doi
2009:doi
2005:119
1966:doi
1928:doi
1887:PMC
1879:doi
1875:105
1840:doi
1836:144
1803:PMC
1785:doi
1741:PMC
1733:doi
1692:doi
1649:doi
1612:doi
1568:PMC
1560:doi
1519:doi
1472:doi
1435:PMC
1427:doi
1380:doi
1376:102
1340:PMC
1264:doi
1216:doi
1204:268
1134:doi
862:.)
822:ATM
810:MRN
791:AFP
553:AFP
485:ATM
441:ATM
240:).
122:ATM
45:or
39:A–T
37:or
6927::
6738::
6696::
5871:SA
5378:OA
5373:HD
5322:PD
5112::
5101::
5087::
5076::
5052::
5041::
5030::
5019::
5004::
5001:10
4928:.
4918:.
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