310:). Also typical are short, sharp muscle contractions called myoclonic jerks. Initial signs of this disorder include delayed psychomotor development with progressive deterioration, other motor disorders, or seizures. The infantile form has the most rapid progression and children live into their mid-childhood years. The gene responsible for infantile NCL has been identified in some cases of juvenile/adult onset. These patients are thought to have some partial enzyme production that leads to a protracted, less severe disease course.
72:
995:
Svennerholm demonstrated a specific ultrastructure and biochemistry for Tay–Sachs disease, and these developments led to the distinct identification and also separation of the NCLs from Tay–Sachs disease by Zeman and
Donahue. At that time, it was proposed that the late-infantile (Jansky–Bielschowsky), the juvenile (Spielmeyer–Vogt), and the adult form (Kufs) were quite different from Tay–Sachs disease with respect to chemical pathology and ultrastructure and also different from other forms of
136:
between 2 and 4 years of age with seizures and deterioration of vision. The maximum age before death for late infantile variant is 10–12 years. Juvenile NCL (JNCL, Batten disease, or
Spielmeyer-Vogt), with a prevalence of one in 100,000, usually arises between 4 and 10 years of age; the first symptoms include considerable vision loss due to retinal dystrophy, with seizures, psychological degeneration, and eventual death in the mid- to late 20s or 30s ensuing. Adult variant NCL (ANCL or
794:, a rare genetic disease that can cause kidney failure if not treated, was reported to be useful in treating the infantile form of NCL. Preliminary results report the drug has completely cleared away storage material from the white blood cells of the first six patients, as well as slowing down the rapid neurodegeneration of infantile NCL. Currently, two drug trials are underway for infantile NCL, both using Cystagon.
554:
159:, each of their children faces a one in four chance of developing NCL. At the same time, each child also faces a one in two chance of inheriting just one copy of the defective gene. Individuals who have only one defective gene are known as carriers, meaning they do not develop the disease, but they can pass the gene on to their own children. The most commonly identified mutations are in the
37:
831:
755:
Between 1.3 and 10% of cases are of the adult form. The age at onset is variable (6–62 yr). Two main clinical subtypes have been described: progressive myoclonus epilepsy (type A) and dementia with motor disturbances, such as cerebellar, extrapyramidal signs and dyskinesia (type B). Unlike the other
746:
deficiency; the overexpression of the defective protein appears to have significant effects on cathepsin D processing, with implications suggesting that accumulation of ATP synthase subunit C would result. Only recently have studies of human patients shown deficiency of lysosomal aspartyl proteinase
1313:
Late
Infantile NCL (LINCL or Jansky-Bielschowsky), on the other hand, initially presents as generalized tonic-clonic or myoclonic seizures beginning at around 2–3 years of age; following this is depressed cognitive development including slow learning, speech delays, and eventual dementia leading to
860:
On
October 20, 2005, the Food and Drug Administration approved a phase-I clinical trial of neural stem cells to treat infantile and late infantile Batten disease. Subsequent approval from an independent review board also approved the stem cell therapy in early March 2006. This treatment will be the
135:
appear normal at birth, but early visual loss leading to complete retinal blindness by the age of 2 years is the first indicator of the disease; by 3 years of age, a vegetative state is reached, and by 4 years, isoelectric encephalograms confirm brain death. Late infantile variant usually manifests
127:
called the neuronal ceroid lipofuscinoses (NCLs) is through the progressive, permanent loss of motor and psychological ability with a severe intracellular accumulation of lipofuscins, with the United States and
Northern European populations having slightly higher frequency with an occurrence of one
994:
Departing from the careful morphological observations of
Spielmeyer, Hurst, and Sjovall and Ericsson, Zeman and Alpert made a determined effort to document the previously suggested pigmentary nature of the neuronal deposits in certain types of storage disorders. Simultaneously, Terry and Korey and
864:
Juvenile NCL has recently been listed on the
Federal Clinical Trials website to test the effectiveness of bone-marrow or stem-cell transplants for this condition. A bone-marrow transplant has been attempted in the late infantile form of NCL with disappointing results; while the transplant may have
818:) called AAVrh.10 began in August 2010, and is once again being conducted by Weill Medical College of Cornell University. Animal models of late infantile NCL showed that the AAVrh.10 delivery system "was much more effective, giving better spread of the gene product and improving survival greatly".
190:
Because vision loss is often an early sign, NCL may be first suspected during an eye exam. An eye doctor can detect a loss of cells within the eye that occurs in the three childhood forms of NCL. However, because such cell loss occurs in other eye diseases, the disorder cannot be diagnosed by this
926:
The first probable instances of this condition were reported in 1826 in a
Norwegian medical journal by Dr. Christian Stengel, who described 4 affected siblings in a small mining community in Norway. Although no pathological studies were performed on these children the clinical descriptions are so
806:
trial using an adenoassociated virus vector called AAV2CUhCLN2 began in June 2004 in an attempt to treat the manifestations of late infantile NCL. The trial was conducted by Weill
Medical College of Cornell University and sponsored by the Nathan's Battle Foundation. In May 2008, the gene therapy
773:-string domain, which is required for membrane targeting/binding, palmitoylation, and oligomerization of the encoded protein cysteine-string protein alpha (CSPα). The mutations dramatically decrease the affinity of CSPα for the membrane. A second report has also located this disease to this gene.
821:
A third gene therapy trial, using the same AAVrh.10 delivery system, began in 2011 and has been expanded to include late infantile NCL patients with moderate tosevere impairment or uncommon genotypes, and uses a novel administration method that reduces general anesthesia time by 50% to minimize
191:
sign alone. Often, an eye specialist or other physician who suspects NCL may refer the child to a neurologist, a doctor who specializes in disease of the brain and nervous system. To diagnose NCL, the neurologist needs the patient's medical history and information from various laboratory tests.
947:
in 1905, who performed extensive clinicopathological studies on several families. Retrospectively, these papers disclose that the authors grouped together different types of the syndrome. Furthermore, Batten, at least for some time, insisted that the condition that he described was distinctly
781:
Currently, no widely accepted treatment can cure, slow down, or halt the symptoms in the great majority of patients with NCL, but seizures may be controlled or reduced with use of antiepileptic drugs. Additionally, physical, speech, and occupational therapies may help affected patients retain
128:
in 10,000. Four classic diagnoses have received the most attention from researchers and the medical field, differentiated from one another by age of symptomatic onset, duration, early-onset manifestations such as blindness or seizures, and the forms which lipofuscin accumulation takes.
844:, has been suggested to possibly slow down the progress of NCL, particularly in the juvenile and late infantile forms. No trial has been officially supported in this venue, however. Currently, the drug is available to NCL families either from Germany, Duke University Medical Center in
364:, JNCL) begins between the ages of 5 and 8 years of age. The typical early signs are progressive vision loss, seizures, ataxia, or clumsiness. This form progresses less rapidly and ends in death in the late teens or early 20s, although some have been known to live into their 30s.
2571:
W. Spielmeyer. Klinische und anatomische
Untersuchungen über eine besondere Form von familiärer amaurotische Idiotie. Freiburg im Breisgau, Gotha, 1907. Reprinted in Nissl: Histologische und histopathologische Arbeiten über die Grosshirnrinde 1908, 2:
807:
given to the recipients reportedly was "safe, and that, on average, it significantly slowed the disease's progression during the 18-month follow-up period" and "suggested that higher doses and a better delivery system may provide greater benefit".
986:, a Swedish psychiatrist and geneticist, presented 115 cases with extensive clinical and genetic documentation and came to the conclusion that the disease now called the Spielmeyer-Sjogren (juvenile) type is genetically separate from Tay–Sachs.
339:) and seizures, along with progressive mental deterioration, though affected children may show mild to severe delays in speech development well before other symptoms appear. This form progresses rapidly and ends in death between ages 8 and 12.
2823:
2808:
700:, is intended to slow loss of walking ability in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as TPP1 deficiency. Brineura is administered into the
2229:"Study of the Safety and Preliminary Effectiveness of Human Central Nervous System (CNS) Stem Cells (HuCNS-SC) in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL) - Full Text View - ClinicalTrials.gov"
103:, and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the
214:
and others. Blood can also be used. These deposits take on characteristic shapes, depending on the variant under which they are said to occur: granular osmophilic deposits (GRODs) are generally characteristic of INCL, while
389:, ANCL) generally begins before the age of 40, causes milder symptoms that progress slowly, and does not cause blindness. Although age of death is variable among affected individuals, this form does shorten life expectancy.
1630:
248:(CT), which uses x-rays and a computer to create a sophisticated picture of the brain's tissues and structures. A CT scan may reveal brain areas that are decaying in NCL patients. An increasingly common tool is
225:
or EEG: An EEG uses special patches placed on the scalp to record electrical currents inside the brain. This helps doctors see telltale patterns in the brain's electrical activity that suggest a patient has
2321:
Claussen M, Heim P, Knispel J, Goebel HH, KohlschĂĽtter A (Feb 1992). "Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders".
861:
first transplant of fetal stem cells performed on humans. The therapy is being developed by Stem Cells Inc and is estimated to have six patients. The treatment was to be carried out in Oregon.
716:
gene on 16p12; of the mutations known to cause JNCL, 85% result from a 1.02-kb deletion, with a loss of amino acids 154–438, while the remaining 15% appear to result from either point or
972:
made these authors change their minds to the extent that they reclassified their respective observations as variants of Tay–Sachs disease, which caused confusion lasting about 50 years.
271:
The older classification of NCL divided the condition into four types (CLN1, CLN2, CLN3, and CLN4) based upon age of onset, while newer classifications divide it by the associated gene.
143:
All the mutations that have been associated with this disease have been linked to genes involved with the neural synapses metabolism – most commonly with the reuse of vesicle proteins.
641:
gene is highly conserved and likely plays a vital role in cell metabolism. In addition, buildup of defective PPT1 in the ER has been shown to cause the increased release of Ca2+. This
198:
Skin or tissue sampling: The doctor can examine a small piece of tissue under a microscope to spot typical NCL deposits. These deposits are found in many different tissues, including
1631:
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5538&ordinalpos=28&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
979:
delineated the late infantile form of NCL. However, all forms were still thought to belong in the group of "familial amaurotic idiocies", of which Tay–Sachs was the prototype.
2185:
Dhar S, Bitting RL, Rylova SN, et al. (Apr 2002). "Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons".
1482:
Mole SE, Williams RE, Goebel HH (September 2005). "Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses".
964:
reported detailed studies on three siblings, who have the Spielmeyer-Sjogren (juvenile) type, which led him to the very firm statement that this malady is not related to
2923:
868:
Trials testing the effectiveness of bone-marrow transplants for infantile NCL in Finland have also been disappointing, with only a slight slowing of disease reported.
165:
gene, which is located on the short arm of chromosome 16 (16p12.1). The normal function of the gene is not presently known, but results in a transmembrane protein.
140:) is less understood and generally manifests milder symptoms; however, while symptoms typically appear around 30 years of age, death usually occurs 10 years later.
3060:
2747:
Santavuori P, Haltia M, Rapola J, Raitta C (Mar 1973). "Infantile type of so-called neuronal ceroid-lipofuscinosis. 1. A clinical study of 15 patients".
1002:
Subsequently, Santavuori and Haltia showed that an infantile form of NCL exists, which Zeman and Dyken had included with the Jansky Bielschowsky type.
155:
disorders; that is, they occur only when a child inherits two copies of the defective gene, one from each parent. When both parents carry one defective
756:
NCLs, retinal degeneration is absent. Pathologically, the ceroid-lipofuscin accumulates mainly in neurons and contains subunit C of the mitochondrial
3168:
306:, INCL): begins between about 6 months and 2 years of age and progresses rapidly. Affected children fail to thrive and have abnormally small heads (
433:
Variant late infantile (late infantile variant, vLINCL) – identified in Costa Rica, South America, Portugal, the United Kingdom and other nations
1904:"Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile ceroid lipofuscinosis"
3244:
2582:
Goebel HH, Gerhard L, Kominami E, Haltia M (July 1996). "Neuronal ceroid-lipofuscinosis—late-infantile or Jansky-Bielschowsky type—revisited".
2916:
2165:"AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis With Uncommon Genotypes or Moderate/Severe Impairment"
2901:
617:
linkages in s-acylated (or palmitoylated) proteins, encouraging their breakdown. Defective polypeptides, however, are unable to exit the
1685:
1524:
1457:
576:
have been associated with ANCL in addition to the infantile and juvenile forms. The mutation typically results in a deficient form of a
2012:
Noskova L, Stranecky V, Hartmannova H, Pristoupilova A, Baresova V, Ivanek R, Hulkova H, Jahnova H, van der Zee J, et al. (2011).
179:, all people who inherit a single copy of the disease gene develop the disease. As a result, no carriers of the gene are unaffected.
3199:
913:
A study in Norway reported an incidence of 3.9 per 100,000 using the years from 1978 to 1999, with a lower rate in earlier decades.
685:
3065:
2086:
2634:
Zeman W, Alpert M (1963). "On the nature of the "stored" lipid substances in juvenile amaurotic idiocy (Batten-Spielmeyer-Vogt)".
2014:"Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis"
3234:
3203:
2940:
2909:
3173:
332:
244:
Brain scans: Imaging can help doctors look for changes in the brain's appearance. The most commonly used imaging technique is
3194:
3006:
581:
2391:
Augestad LB, Flanders WD (Nov 2006). "Occurrence of and mortality from childhood neuronal ceroid lipofuscinoses in norway".
2289:
735:(after its apparent connections to Batten's disease, or JNCL), have suggested that the protein may play a role in lysosomal
303:
1877:
3249:
3115:
3110:
1132:"CLN3L, a novel protein related to the Batten disease protein, is overexpressed in Cln3-/- mice and in Batten disease"
944:
252:, which uses a combination of magnetic fields and radio waves, instead of radiation, to create a picture of the brain.
124:
219:
profiles, fingerprint profiles, and mixed-type inclusions are typically found in LINCL, JNCL, and ANCL, respectively.
2936:
689:
470:
249:
88:
85:
2522:
Batten, F. E. (1902). "Cerebral degeneration with symmetrical changes in the maculae in two members of a family".
1953:
Benitez BA, Alvarado D, Cai Y, Mayo K, Chakraverty S, Norton J, Morris JC, Sands MS, Goate A, et al. (2011).
255:
Enzyme assay: A recent development in diagnosis of NCL is the use of enzyme assays that look for specific missing
2932:
2164:
2142:
2064:
1173:"Neuronal ceroid lipofuscinoses are connected at molecular level: interaction of CLN5 protein with CLN2 and CLN3"
625:; further analyses of this pathway could serve to categorize INCL among lysosomal enzyme deficiencies. The human
3056:
2143:"Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis"
1378:
Isosomppi, J.; et al. (2002). "Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein".
2838:
1704:
Lyly, Annina; Von Schantz, C; Salonen, T; Kopra, O; Saarela, J; Jauhiainen, M; Kyttälä, A; Jalanko, A (2007).
885:
704:
by infusion via a surgically implanted reservoir and catheter in the head (intraventricular access device).
670:
3239:
3213:
2944:
2712:
Svennerholm L (November 1962). "The chemical structure of normal human brain and Tay–Sachs gangliosides".
1806:
1798:
845:
234:
3001:
1283:"PPT1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL"
965:
949:
3026:
2889:
2065:"Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis"
1794:
618:
653:, eventually leading to an accumulation of cleft and uncleft poly(ADP-ribose) polymerase and eventual
2243:
3075:
2670:
2356:
Cardona F, Rosati E (Jun 1995). "Neuronal ceroid-lipofuscinoses in Italy: an epidemiological study".
2112:
1966:
681:
groups of partially unfolded proteins. Mutations of this gene typically result in a LINCL phenotype.
222:
71:
2827:
2307:
1542:"Kufs Disease, the Major Adult Form of Neuronal Ceroid Lipofuscinosis, Caused by Mutations in CLN6"
896:
On April 27, 2017, the U.S. FDA approved cerliponase alfa as the first specific treatment for NCL.
810:
A second gene therapy trial for late infantile NCL using an adenoassociated virus derived from the
717:
701:
610:
603:
565:
245:
238:
44:
3120:
2992:
2987:
2694:
2607:
2416:
2271:
2210:
2113:"Gene therapy trial offers new hope for Batten disease, a fatal neurological disease in children"
1780:
1507:
1053:
961:
957:
953:
928:
173:
169:
2661:
Terry RD, Korey SR (Dec 1960). "Membranous cytoplasmic granules in infantile amaurotic idiocy".
1590:
983:
969:
769:
gene – one with a transversion and the other with a deletion mutation. The mutations occur in a
335:, LINCL) begins between ages 2 and 4. The typical early signs are loss of muscle coordination (
2867:
2764:
2729:
2686:
2643:
2599:
2504:
2451:
2408:
2373:
2338:
2263:
2202:
2043:
1994:
1935:
1856:
1772:
1737:
1668:
1612:
1571:
1499:
1439:
1395:
1360:
1304:
1258:
1202:
1153:
1106:
1034:
881:
865:
slowed the onset of the disease, the child eventually developed the disease and died in 1998.
782:
functioning for as long as possible. Several experimental treatments are under investigation.
573:
561:
517:
60:
1955:"Exome-sequencing confirms DNAJC5 mutations as cause of Adult Neuronal Ceroid-Lipofuscinosis"
3071:
2996:
2953:
2756:
2721:
2678:
2591:
2554:
2443:
2400:
2365:
2330:
2255:
2194:
2033:
2025:
1984:
1974:
1925:
1915:
1846:
1838:
1764:
1727:
1717:
1658:
1602:
1561:
1553:
1491:
1429:
1387:
1350:
1342:
1294:
1248:
1240:
1192:
1184:
1143:
1096:
996:
976:
940:
815:
697:
1065:
693:
622:
262:
for infantile and late infantile versions only. This is a quick and easy diagnostic test.
2674:
2474:
2090:
1970:
3207:
3178:
3146:
3124:
3096:
2974:
2595:
2038:
2013:
1989:
1954:
1732:
1705:
1566:
1541:
1355:
1330:
1244:
1101:
1085:"Accumulation of the adenosine triphosphate synthase subunit c in the mnd mutant mouse"
1084:
811:
712:
All mutations resulting in the juvenile variant of NCL have been shown to occur at the
415:
Finnish late infantile (Finnish late infantile variant, vLINCL) – identified in Finland
361:
152:
2832:
1930:
1903:
1851:
1822:
1253:
1228:
1197:
1172:
490:
Turkish late infantile (Turkish late infantile variant, vLINCL) – identified in Turkey
3228:
3049:
3041:
3030:
2760:
2725:
2434:
Haltia M (October 2006). "The neuronal ceroid-lipofuscinoses: from past to present".
2244:"Hematopoietic stem cell transplantation in infantile neuronal ceroid lipofuscinosis"
1458:"Batten Disease Fact Sheet | National Institute of Neurological Disorders and Stroke"
646:
65:
2878:
2611:
2485:
C. Stengel. Beretning om et mærkeligt Sygdomstilfelde hos fire Sødskende. Eyr, 1826.
2420:
2275:
2214:
688:
approved cerliponase alfa (Brineura) as the first specific treatment for NCL. It is
3091:
2698:
1790:
1755:
Gupta, P.; Hofmann, S. L. (2002). "NCL/Batten disease: the lysosomal proteinoses".
1511:
803:
757:
606:(M6P) receptor-mediated pathway. Here, the protein appears to function in removing
553:
386:
307:
137:
48:
2228:
168:
Adult NCL may be inherited as an autosomal recessive (Kufs), or less often, as an
2843:
2447:
2404:
2293:
1979:
1115:
There are more than eight variants of NCL, found in 1 in 12,500 people worldwide.
1027:"Neuronal Ceroid-Lipofuscinoses – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY"
3134:
2983:
2969:
2862:
1784:
743:
739:
642:
595:
216:
207:
176:
2029:
1557:
131:
In the early infantile variant of NCL (also called INCL or Santavuori-Haltia),
36:
2817:
2785:
1647:"Loci for classical and a variant LINCL map to chromosomes 11p15 and 15q21-23"
1495:
1026:
841:
834:
791:
592:
112:
92:
52:
1434:
1417:
3106:
3086:
3018:
2873:
2469:
2369:
2334:
2308:"eMedicine – Neuronal Ceroid Lipofuscinoses : Article by Celia H Chang"
1188:
1022:
654:
650:
614:
607:
588:
2733:
2690:
2647:
2508:
2455:
2412:
2267:
2206:
2047:
1998:
1939:
1920:
1860:
1776:
1741:
1722:
1616:
1607:
1575:
1503:
1443:
1399:
1391:
1364:
1308:
1206:
1157:
1148:
1131:
1038:
904:
Incidence can vary greatly from type-to-type, and from country-to-country.
274:
CLN4 (unlike CLN1, CLN2, and CLN3) has not been mapped to a specific gene.
2768:
2603:
2377:
2342:
2259:
1768:
1672:
1663:
1646:
1346:
1262:
1110:
724:
gene codes for a protein with no known function, but studies of the yeast
3142:
2958:
2884:
1802:
1299:
1282:
877:
770:
732:
728:
599:
577:
256:
227:
96:
2800:
84:
is the general name for a family of at least eight genetically separate
1331:"Identification of CLN2 mutations shows Canadian specific NCL2 alleles"
849:
830:
132:
99:. Their name comes from the word stem "lipo-", which is a variation on
2682:
2558:
2198:
742:. Furthermore, recent studies have also implied the protein's role in
471:
Northern epilepsy, progressive epilepsy with mental retardation (EPMR)
2812:
1589:
Schulz A, Mousallem T, Venkataramani M, et al. (February 2006).
765:
405:
336:
259:
211:
203:
108:
2543:"Über familiäre amaurotische Idiotie und verwandte Krankheitsbilder"
2542:
2524:
Transactions of the Ophthalmological Societies of the United Kingdom
95:) in the body's tissues. These lipopigments are made up of fats and
1842:
182:
Many authorities refer to the NCLs collectively as Batten disease.
829:
763:
Two independent families have been shown to have mutations in the
678:
459:
104:
100:
2242:
Lönnqvist T, Vanhanen SL, Vettenranta K, et al. (Oct 2001).
907:
In Germany, one study reported an incidence of 1.28 per 100,000.
1689:
1528:
674:
572:
gene (located at 1p32) always induce classical INCL, while some
535:
530:
511:
498:
493:
480:
475:
454:
441:
436:
423:
418:
402:
396:
392:
372:
367:
347:
342:
318:
313:
286:
199:
161:
156:
123:
The classic characterization of the group of neurodegenerative,
2905:
2786:
GeneReviews/NCBI/NIH/UW entry on Neuronal ceroid-Lipofuscinosis
1801:
at amino acid 208 of 563 (7). The deficiency of this lysosomal
888:, may be useful in slowing down the progress of juvenile NCL.
1130:
Narayan SB, Pastor JV, Mitchison HM, Bennett MJ (Aug 2004).
910:
A study in Italy reported an incidence of 0.56 per 100,000.
1878:"FDA approves first treatment for a form of Batten disease"
1591:"The CLN9 protein, a regulator of dihydroceramide synthase"
968:. Subsequently, however, the pathomorphological studies of
736:
241:, can detect various eye problems common in childhood NCLs.
233:
Electrical studies of the eyes: These tests, which include
2624:
K. G. T. Sjögren. Die juvenile amaurotische Idiotie. 1931.
1827:-encoded transmembrane cause variant NCL in man and mouse"
1171:
Vesa J, Chin MH, Oelgeschläger K, et al. (Jul 2002).
2290:"BDSRA – Batten Disease Support and Research Association"
1706:"Glycosylation, transport, and complex formation of PPT1"
91:
that result from excessive accumulation of lipopigments (
840:
A painkiller available in several European countries,
2137:
2135:
2133:
876:
In late 2007, Dr. David Pearce et al. reported that
2790:
3187:
3159:
3132:
3084:
3039:
3016:
2967:
2952:
2853:
2794:
649:membrane permeability and subsequent activation of
59:
26:
21:
2059:
2057:
1789:Two mutations common to this gene are a G-to-C
939:More fundamental observations were reported by
696:technology. The active ingredient in Brineura,
1314:death, usually between 14 and 36 years of age.
669:gene encodes a 46kDa protein called lysosomal
598:that is typically targeted for transport into
2917:
8:
2547:Monatsschrift fĂĽr Psychiatrie und Neurologie
677:), which cleaves tripeptides from terminal
2964:
2924:
2910:
2902:
2791:
2087:"Nathan's Battle – Clinical Trial Efforts"
1872:
1870:
527:CLN10 (congenital, cathepsin D deficiency)
516:Unknown, but possibly regulator of dihydro
70:
35:
18:
2037:
1988:
1978:
1929:
1919:
1850:
1731:
1721:
1662:
1606:
1565:
1433:
1354:
1298:
1252:
1196:
1147:
1100:
552:
276:
194:Diagnostic tests used for NCLs include:
1640:
1638:
1416:Persaud-Sawin, D.; et al. (2002).
1011:
848:, or the Hospital for Sick Children in
1699:
1697:
1411:
1409:
1229:"Human palmitoyl protein thioesterase"
1125:
1123:
1078:
1076:
1061:
1051:
1025:; Williams, Ruth E. (1 January 1993).
1540:Arsov, T; et al. (13 May 2011).
1324:
1322:
1276:
1274:
1272:
1222:
1220:
1218:
1216:
1033:. University of Washington, Seattle.
7:
2358:American Journal of Medical Genetics
2323:American Journal of Medical Genetics
931:(juvenile) type is fully justified.
629:gene shows 91% similarity to bovine
1686:Online Mendelian Inheritance in Man
1525:Online Mendelian Inheritance in Man
1227:Hellstein, E.; et al. (1996).
1017:
1015:
927:succinct that the diagnosis of the
645:-altering event leads to increased
2596:10.1111/j.1750-3639.1996.tb00850.x
2018:American Journal of Human Genetics
1831:American Journal of Human Genetics
1546:American Journal of Human Genetics
1245:10.1002/j.1460-2075.1996.tb00909.x
14:
3200:Cholesteryl ester storage disease
1902:Fossale, E.; et al. (2004).
731:, the product of which is called
686:U.S. Food and Drug Administration
3204:Lysosomal acid lipase deficiency
1418:"Motifs within the CLN3 protein"
822:potential adverse side effects.
508:Identified in Germany and Serbia
2145:. National Institutes of Health
2067:. National Institutes of Health
1645:Sharp, J.; et al. (1997).
1083:Pardo, C.; et al. (1994).
637:; these data indicate that the
3195:Cerebrotendinous xanthomatosis
1797:, which prematurely terminate
1031:Neuronal Ceroid-Lipofuscinoses
960:type A. Around the same time,
952:, the prototype of a neuronal
790:In 2001, a drug used to treat
582:palmitoyl protein thioesterase
82:Neuronal ceroid lipofuscinosis
22:Neuronal ceroid lipofuscinosis
1:
3245:Autosomal recessive disorders
3116:Multiple sulfatase deficiency
2714:Biochem. Biophys. Res. Commun
1821:Gao, H.; et al. (2002).
1805:, then, results in increased
1281:Kim, S.; et al. (2006).
151:Childhood NCLs are generally
3111:Metachromatic leukodystrophy
2761:10.1016/0022-510X(73)90075-0
2726:10.1016/0006-291X(62)90030-X
2448:10.1016/j.bbadis.2006.06.010
2405:10.1177/08830738060210110801
1980:10.1371/journal.pone.0026741
1329:Ju, W.; et al. (2002).
884:medication commonly used in
55:granules in blue and yellow.
3174:Jansky–Bielschowsky disease
1335:Journal of Medical Genetics
333:Jansky–Bielschowsky disease
125:lysosomal storage disorders
3266:
2933:Lysosomal storage diseases
2495:Brean A (April 2004). "".
2030:10.1016/j.ajhg.2011.07.003
1558:10.1016/j.ajhg.2011.04.004
892:Enzyme replacement therapy
690:enzyme replacement therapy
633:and 85% similarity to rat
250:magnetic resonance imaging
89:lysosomal storage diseases
2497:Tidsskr. Nor. Laegeforen.
1496:10.1007/s10048-005-0218-3
621:(ER), most likely due to
304:Santavuori–Haltia disease
43:
34:
1629:NCBI Entrez Gene: PPT1
3235:Lipid storage disorders
2945:Lipid storage disorders
2370:10.1002/ajmg.1320570206
2335:10.1002/ajmg.1320420422
1189:10.1091/mbc.E02-01-0031
886:bone-marrow transplants
684:On April 27, 2017, the
671:tripeptidyl peptidase I
235:visual-evoked responses
172:(Parry's) disorder. In
3214:Sea-blue histiocytosis
2436:Biochim. Biophys. Acta
1921:10.1186/1471-2202-5-57
1823:"Mutations in a novel
1723:10.1186/1471-2121-8-22
1608:10.1074/jbc.M509483200
1435:10.1093/hmg/11.18.2129
846:Durham, North Carolina
837:
558:
3027:Globotriaosylceramide
2553:(2): 161–71, 310–57.
2260:10.1212/wnl.57.8.1411
1769:10.1038/sj.mp.4001127
1347:10.1136/jmg.39.11.822
833:
692:manufactured through
619:endoplasmic reticulum
556:
3250:Congenital disorders
3057:Niemann–Pick disease
1392:10.1093/hmg/11.8.885
1149:10.1093/brain/awh195
718:frameshift mutations
223:Electroencephalogram
2675:1960Natur.188.1000T
2187:Annals of Neurology
2024:(241–252): 241–52.
1971:2011PLoSO...626741B
1690:NCL1, CLN1 - 256730
1664:10.1093/hmg/6.4.591
751:Adult dominant form
702:cerebrospinal fluid
661:Late infantile form
604:mannose 6-phosphate
557:Mannose-6-phosphate
246:computed tomography
153:autosomal recessive
3121:Galactocerebroside
2993:GM2 gangliosidoses
2988:GM1 gangliosidoses
2854:External resources
2231:. 13 January 2015.
1300:10.1093/hmg/ddl078
962:Walther Spielmeyer
958:GM2 gangliosidosis
956:now identified as
954:lysosomal disorder
929:Spielmeyer-Sjogren
872:Immunosuppressants
838:
574:missense mutations
559:
329:Late infantile NCL
239:electroretinograms
174:autosomal dominant
170:autosomal dominant
119:Signs and symptoms
3222:
3221:
3155:
3154:
3076:Gaucher's disease
3002:Tay–Sachs disease
2899:
2898:
2683:10.1038/1881000a0
2559:10.1159/000213427
2541:Vogt, H. (1905).
2199:10.1002/ana.10143
2117:Cornell Chronicle
1462:www.ninds.nih.gov
1428:(18): 2129–2142.
1233:Eur Mol Bio Org J
1142:(Pt 8): 1748–54.
966:Tay–Sachs disease
950:Tay–Sachs disease
882:immunosuppressant
568:mutations in the
541:
540:
518:ceramide synthase
86:neurodegenerative
79:
78:
16:Medical condition
3257:
3072:Glucocerebroside
3061:SMPD1-associated
2997:Sandhoff disease
2965:
2954:Sphingolipidoses
2941:lipid metabolism
2926:
2919:
2912:
2903:
2792:
2773:
2772:
2744:
2738:
2737:
2709:
2703:
2702:
2669:(4755): 1000–2.
2658:
2652:
2651:
2631:
2625:
2622:
2616:
2615:
2579:
2573:
2569:
2563:
2562:
2538:
2532:
2531:
2519:
2513:
2512:
2499:(in Norwegian).
2492:
2486:
2483:
2477:
2466:
2460:
2459:
2431:
2425:
2424:
2388:
2382:
2381:
2353:
2347:
2346:
2318:
2312:
2311:
2304:
2298:
2297:
2292:. Archived from
2286:
2280:
2279:
2239:
2233:
2232:
2225:
2219:
2218:
2182:
2176:
2175:
2173:
2171:
2161:
2155:
2154:
2152:
2150:
2139:
2128:
2127:
2125:
2123:
2108:
2102:
2101:
2099:
2098:
2089:. Archived from
2083:
2077:
2076:
2074:
2072:
2061:
2052:
2051:
2041:
2009:
2003:
2002:
1992:
1982:
1950:
1944:
1943:
1933:
1923:
1908:BMC Neuroscience
1899:
1893:
1892:
1890:
1888:
1874:
1865:
1864:
1854:
1818:
1812:
1811:
1752:
1746:
1745:
1735:
1725:
1710:BMC Cell Biology
1701:
1692:
1683:
1677:
1676:
1666:
1642:
1633:
1627:
1621:
1620:
1610:
1586:
1580:
1579:
1569:
1537:
1531:
1522:
1516:
1515:
1479:
1473:
1472:
1470:
1468:
1454:
1448:
1447:
1437:
1413:
1404:
1403:
1375:
1369:
1368:
1358:
1326:
1317:
1316:
1302:
1278:
1267:
1266:
1256:
1224:
1211:
1210:
1200:
1168:
1162:
1161:
1151:
1127:
1118:
1117:
1104:
1080:
1071:
1069:
1063:
1059:
1057:
1049:
1047:
1045:
1019:
997:sphingolipidoses
977:Max Bielschowsky
943:in 1903, and by
816:Old World monkey
720:. The wild-type
698:cerliponase alfa
277:
75:
74:
51:showing stained
39:
19:
3265:
3264:
3260:
3259:
3258:
3256:
3255:
3254:
3225:
3224:
3223:
3218:
3183:
3151:
3128:
3089:
3080:
3035:
3031:Fabry's disease
3012:
2972:
2956:
2948:
2930:
2900:
2895:
2894:
2849:
2848:
2803:
2782:
2777:
2776:
2746:
2745:
2741:
2711:
2710:
2706:
2660:
2659:
2655:
2633:
2632:
2628:
2623:
2619:
2581:
2580:
2576:
2570:
2566:
2540:
2539:
2535:
2521:
2520:
2516:
2494:
2493:
2489:
2484:
2480:
2467:
2463:
2433:
2432:
2428:
2393:J. Child Neurol
2390:
2389:
2385:
2355:
2354:
2350:
2320:
2319:
2315:
2310:. 15 July 2021.
2306:
2305:
2301:
2288:
2287:
2283:
2241:
2240:
2236:
2227:
2226:
2222:
2184:
2183:
2179:
2169:
2167:
2163:
2162:
2158:
2148:
2146:
2141:
2140:
2131:
2121:
2119:
2111:Klein, Andrew.
2110:
2109:
2105:
2096:
2094:
2085:
2084:
2080:
2070:
2068:
2063:
2062:
2055:
2011:
2010:
2006:
1952:
1951:
1947:
1901:
1900:
1896:
1886:
1884:
1876:
1875:
1868:
1820:
1819:
1815:
1754:
1753:
1749:
1703:
1702:
1695:
1684:
1680:
1644:
1643:
1636:
1628:
1624:
1588:
1587:
1583:
1539:
1538:
1534:
1523:
1519:
1481:
1480:
1476:
1466:
1464:
1456:
1455:
1451:
1415:
1414:
1407:
1377:
1376:
1372:
1341:(11): 822–825.
1328:
1327:
1320:
1293:(10): 1586–90.
1280:
1279:
1270:
1226:
1225:
1214:
1170:
1169:
1165:
1129:
1128:
1121:
1082:
1081:
1074:
1060:
1050:
1043:
1041:
1021:
1020:
1013:
1008:
992:
984:Torsten Sjögren
970:Károly Schaffer
948:different from
937:
924:
919:
902:
894:
874:
858:
828:
800:
788:
779:
753:
710:
694:recombinant DNA
663:
551:
546:
269:
188:
149:
121:
115:, and kidneys.
69:
17:
12:
11:
5:
3263:
3261:
3253:
3252:
3247:
3242:
3237:
3227:
3226:
3220:
3219:
3217:
3216:
3211:
3208:Wolman disease
3197:
3191:
3189:
3185:
3184:
3182:
3181:
3179:Batten disease
3176:
3171:
3165:
3163:
3157:
3156:
3153:
3152:
3150:
3149:
3147:Farber disease
3139:
3137:
3130:
3129:
3127:
3125:Krabbe disease
3118:
3113:
3104:
3102:
3101:
3100:
3097:leukodystrophy
3082:
3081:
3079:
3078:
3069:
3063:
3046:
3044:
3037:
3036:
3034:
3033:
3023:
3021:
3014:
3013:
3011:
3010:
3004:
2999:
2990:
2980:
2978:
2975:gangliosidoses
2962:
2950:
2949:
2931:
2929:
2928:
2921:
2914:
2906:
2897:
2896:
2893:
2892:
2881:
2870:
2858:
2857:
2855:
2851:
2850:
2847:
2846:
2835:
2820:
2804:
2799:
2798:
2796:
2795:Classification
2789:
2788:
2781:
2780:External links
2778:
2775:
2774:
2739:
2704:
2653:
2626:
2617:
2574:
2564:
2533:
2514:
2487:
2478:
2461:
2426:
2399:(11): 917–22.
2383:
2348:
2313:
2299:
2296:on 2008-07-24.
2281:
2234:
2220:
2177:
2156:
2129:
2103:
2078:
2053:
2004:
1965:(11): e26741.
1945:
1894:
1866:
1843:10.1086/338190
1813:
1757:Mol Psychiatry
1747:
1693:
1678:
1634:
1622:
1601:(5): 2784–94.
1581:
1532:
1517:
1474:
1449:
1405:
1370:
1318:
1268:
1239:(19): 5240–5.
1212:
1183:(7): 2410–20.
1163:
1119:
1095:(4): 829–835.
1072:
1062:|journal=
1010:
1009:
1007:
1004:
991:
988:
936:
933:
923:
920:
918:
915:
901:
898:
893:
890:
873:
870:
857:
854:
827:
824:
814:(a species of
812:rhesus macaque
799:
796:
787:
784:
778:
775:
752:
749:
709:
706:
662:
659:
591:PPT1 is a 306-
580:enzyme called
550:
549:Infantile form
547:
545:
542:
539:
538:
533:
528:
525:
521:
520:
514:
509:
506:
502:
501:
496:
491:
488:
484:
483:
478:
473:
467:
463:
462:
457:
452:
449:
445:
444:
439:
434:
431:
427:
426:
421:
416:
413:
409:
408:
400:
390:
380:
376:
375:
370:
365:
362:Batten disease
355:
351:
350:
345:
340:
326:
322:
321:
316:
311:
297:
293:
292:
289:
284:
281:
268:
265:
264:
263:
253:
242:
231:
220:
187:
184:
148:
145:
120:
117:
77:
76:
63:
57:
56:
45:Confocal image
41:
40:
32:
31:
28:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
3262:
3251:
3248:
3246:
3243:
3241:
3240:Rare diseases
3238:
3236:
3233:
3232:
3230:
3215:
3212:
3209:
3205:
3201:
3198:
3196:
3193:
3192:
3190:
3186:
3180:
3177:
3175:
3172:
3170:
3167:
3166:
3164:
3162:
3158:
3148:
3144:
3141:
3140:
3138:
3136:
3131:
3126:
3122:
3119:
3117:
3114:
3112:
3108:
3105:
3103:
3098:
3095:
3094:
3093:
3088:
3083:
3077:
3073:
3070:
3067:
3064:
3062:
3058:
3055:
3054:phospholipid:
3051:
3050:Sphingomyelin
3048:
3047:
3045:
3043:
3042:sphingomyelin
3038:
3032:
3028:
3025:
3024:
3022:
3020:
3015:
3008:
3005:
3003:
3000:
2998:
2994:
2991:
2989:
2985:
2982:
2981:
2979:
2976:
2971:
2966:
2963:
2960:
2955:
2951:
2946:
2942:
2938:
2937:Inborn errors
2934:
2927:
2922:
2920:
2915:
2913:
2908:
2907:
2904:
2891:
2887:
2886:
2882:
2880:
2876:
2875:
2871:
2869:
2865:
2864:
2860:
2859:
2856:
2852:
2845:
2841:
2840:
2836:
2834:
2830:
2829:
2825:
2821:
2819:
2815:
2814:
2810:
2806:
2805:
2802:
2797:
2793:
2787:
2784:
2783:
2779:
2770:
2766:
2762:
2758:
2755:(3): 257–67.
2754:
2750:
2743:
2740:
2735:
2731:
2727:
2723:
2720:(5): 436–41.
2719:
2715:
2708:
2705:
2700:
2696:
2692:
2688:
2684:
2680:
2676:
2672:
2668:
2664:
2657:
2654:
2649:
2645:
2641:
2637:
2636:Ann Histochim
2630:
2627:
2621:
2618:
2613:
2609:
2605:
2601:
2597:
2593:
2589:
2585:
2578:
2575:
2568:
2565:
2560:
2556:
2552:
2548:
2544:
2537:
2534:
2529:
2525:
2518:
2515:
2510:
2506:
2502:
2498:
2491:
2488:
2482:
2479:
2476:
2475:Who Named It?
2472:
2471:
2465:
2462:
2457:
2453:
2449:
2445:
2442:(10): 850–6.
2441:
2437:
2430:
2427:
2422:
2418:
2414:
2410:
2406:
2402:
2398:
2394:
2387:
2384:
2379:
2375:
2371:
2367:
2363:
2359:
2352:
2349:
2344:
2340:
2336:
2332:
2328:
2324:
2317:
2314:
2309:
2303:
2300:
2295:
2291:
2285:
2282:
2277:
2273:
2269:
2265:
2261:
2257:
2254:(8): 1411–6.
2253:
2249:
2245:
2238:
2235:
2230:
2224:
2221:
2216:
2212:
2208:
2204:
2200:
2196:
2193:(4): 448–66.
2192:
2188:
2181:
2178:
2166:
2160:
2157:
2144:
2138:
2136:
2134:
2130:
2118:
2114:
2107:
2104:
2093:on 2008-05-09
2092:
2088:
2082:
2079:
2066:
2060:
2058:
2054:
2049:
2045:
2040:
2035:
2031:
2027:
2023:
2019:
2015:
2008:
2005:
2000:
1996:
1991:
1986:
1981:
1976:
1972:
1968:
1964:
1960:
1956:
1949:
1946:
1941:
1937:
1932:
1927:
1922:
1917:
1913:
1909:
1905:
1898:
1895:
1883:
1879:
1873:
1871:
1867:
1862:
1858:
1853:
1848:
1844:
1840:
1837:(2): 324–35.
1836:
1832:
1828:
1826:
1817:
1814:
1810:
1808:
1804:
1800:
1796:
1793:and a C-to-T
1792:
1786:
1782:
1778:
1774:
1770:
1766:
1762:
1758:
1751:
1748:
1743:
1739:
1734:
1729:
1724:
1719:
1715:
1711:
1707:
1700:
1698:
1694:
1691:
1687:
1682:
1679:
1674:
1670:
1665:
1660:
1656:
1652:
1651:Hum Mol Genet
1648:
1641:
1639:
1635:
1632:
1626:
1623:
1618:
1614:
1609:
1604:
1600:
1596:
1595:J. Biol. Chem
1592:
1585:
1582:
1577:
1573:
1568:
1563:
1559:
1555:
1552:(5): 566–73.
1551:
1547:
1543:
1536:
1533:
1530:
1526:
1521:
1518:
1513:
1509:
1505:
1501:
1497:
1493:
1490:(3): 107–26.
1489:
1485:
1484:Neurogenetics
1478:
1475:
1463:
1459:
1453:
1450:
1445:
1441:
1436:
1431:
1427:
1423:
1422:Hum Mol Genet
1419:
1412:
1410:
1406:
1401:
1397:
1393:
1389:
1386:(8): 885–91.
1385:
1381:
1380:Hum Mol Genet
1374:
1371:
1366:
1362:
1357:
1352:
1348:
1344:
1340:
1336:
1332:
1325:
1323:
1319:
1315:
1310:
1306:
1301:
1296:
1292:
1288:
1287:Hum Mol Genet
1284:
1277:
1275:
1273:
1269:
1264:
1260:
1255:
1250:
1246:
1242:
1238:
1234:
1230:
1223:
1221:
1219:
1217:
1213:
1208:
1204:
1199:
1194:
1190:
1186:
1182:
1178:
1177:Mol Biol Cell
1174:
1167:
1164:
1159:
1155:
1150:
1145:
1141:
1137:
1133:
1126:
1124:
1120:
1116:
1112:
1108:
1103:
1098:
1094:
1090:
1086:
1079:
1077:
1073:
1067:
1055:
1040:
1036:
1032:
1028:
1024:
1023:Mole, Sara E.
1018:
1016:
1012:
1005:
1003:
1000:
998:
990:1950 to today
989:
987:
985:
980:
978:
973:
971:
967:
963:
959:
955:
951:
946:
945:Heinrich Vogt
942:
934:
932:
930:
921:
916:
914:
911:
908:
905:
899:
897:
891:
889:
887:
883:
879:
871:
869:
866:
862:
855:
853:
851:
847:
843:
836:
832:
825:
823:
819:
817:
813:
808:
805:
797:
795:
793:
785:
783:
776:
774:
772:
768:
767:
761:
759:
750:
748:
747:cathepsin D.
745:
741:
738:
734:
730:
727:
723:
719:
715:
708:Juvenile form
707:
705:
703:
699:
695:
691:
687:
682:
680:
676:
672:
668:
660:
658:
656:
652:
648:
647:mitochondrial
644:
640:
636:
632:
628:
624:
620:
616:
612:
609:
605:
601:
597:
594:
590:
585:
583:
579:
575:
571:
567:
563:
555:
548:
543:
537:
534:
532:
529:
526:
523:
522:
519:
515:
513:
510:
507:
504:
503:
500:
497:
495:
492:
489:
486:
485:
482:
479:
477:
474:
472:
468:
465:
464:
461:
458:
456:
453:
450:
447:
446:
443:
440:
438:
435:
432:
429:
428:
425:
422:
420:
417:
414:
411:
410:
407:
404:
401:
398:
394:
391:
388:
384:
381:
378:
377:
374:
371:
369:
366:
363:
359:
356:
353:
352:
349:
346:
344:
341:
338:
334:
330:
327:
324:
323:
320:
317:
315:
312:
309:
305:
301:
300:Infantile NCL
298:
295:
294:
290:
288:
285:
282:
279:
278:
275:
272:
266:
261:
258:
254:
251:
247:
243:
240:
236:
232:
229:
224:
221:
218:
213:
209:
205:
201:
197:
196:
195:
192:
185:
183:
180:
178:
175:
171:
166:
164:
163:
158:
154:
146:
144:
141:
139:
138:Kuf's disease
134:
129:
126:
118:
116:
114:
110:
106:
102:
98:
94:
90:
87:
83:
73:
67:
66:Endocrinology
64:
62:
58:
54:
50:
46:
42:
38:
33:
29:
25:
20:
3160:
3092:sulfatidoses
3053:
2883:
2872:
2861:
2837:
2822:
2807:
2752:
2749:J Neurol Sci
2748:
2742:
2717:
2713:
2707:
2666:
2662:
2656:
2639:
2635:
2629:
2620:
2590:(3): 225–8.
2587:
2584:Brain Pathol
2583:
2577:
2567:
2550:
2546:
2536:
2527:
2523:
2517:
2503:(7): 970–1.
2500:
2496:
2490:
2481:
2468:
2464:
2439:
2435:
2429:
2396:
2392:
2386:
2364:(2): 142–3.
2361:
2357:
2351:
2329:(4): 536–8.
2326:
2322:
2316:
2302:
2294:the original
2284:
2251:
2247:
2237:
2223:
2190:
2186:
2180:
2168:. Retrieved
2159:
2147:. Retrieved
2120:. Retrieved
2116:
2106:
2095:. Retrieved
2091:the original
2081:
2069:. Retrieved
2021:
2017:
2007:
1962:
1958:
1948:
1911:
1907:
1897:
1885:. Retrieved
1881:
1834:
1830:
1824:
1816:
1791:transversion
1788:
1763:(5): 434–6.
1760:
1756:
1750:
1713:
1709:
1681:
1657:(4): 591–5.
1654:
1650:
1625:
1598:
1594:
1584:
1549:
1545:
1535:
1520:
1487:
1483:
1477:
1465:. Retrieved
1461:
1452:
1425:
1421:
1383:
1379:
1373:
1338:
1334:
1312:
1290:
1286:
1236:
1232:
1180:
1176:
1166:
1139:
1135:
1114:
1092:
1088:
1042:. Retrieved
1030:
1001:
993:
981:
975:In 1913–14,
974:
941:F. E. Batten
938:
935:1900 to 1950
925:
922:19th century
912:
909:
906:
903:
900:Epidemiology
895:
875:
867:
863:
859:
839:
820:
809:
804:gene therapy
801:
798:Gene therapy
789:
780:
764:
762:
758:ATP synthase
754:
725:
721:
713:
711:
683:
666:
664:
638:
634:
630:
626:
613:by cleaving
586:
569:
560:
524:Type 10
387:Kufs disease
382:
358:Juvenile NCL
357:
328:
308:microcephaly
299:
273:
270:
193:
189:
181:
167:
160:
150:
142:
130:
122:
81:
80:
49:motor neuron
47:of a spinal
3135:sphingosine
2984:Ganglioside
2970:ganglioside
2863:MedlinePlus
2170:16 December
2149:16 December
2071:16 December
1882:www.fda.gov
1799:translation
1467:27 December
1089:Am J Pathol
1070:update 2013
1044:11 December
744:cathepsin D
740:homeostasis
643:homeostasis
596:polypeptide
283:Description
217:curvilinear
208:conjunctiva
177:inheritance
27:Other names
3229:Categories
3007:AB variant
2097:2008-05-10
1795:transition
1006:References
856:Stem cells
842:flupirtine
835:Flupirtine
826:Flupirtine
792:cystinosis
623:misfolding
593:amino acid
584:1 (PPT1).
566:frameshift
113:myocardium
93:lipofuscin
53:lipofuscin
3169:Infantile
3107:Sulfatide
3087:sulfatide
3019:globoside
2879:neuro/498
2874:eMedicine
2642:: 255–7.
2530:: 386–90.
2248:Neurology
1807:subunit C
1064:ignored (
1054:cite book
982:In 1931,
777:Treatment
655:apoptosis
651:caspase-9
615:thioester
608:palmitate
600:lysosomes
589:wild-type
578:lysosomal
544:Mutations
383:Adult NCL
257:lysosomal
186:Diagnosis
61:Specialty
3143:Ceramide
2959:ceramide
2885:Orphanet
2734:13979552
2691:13776040
2648:14171739
2612:28827692
2572:193–213.
2509:15088608
2456:16908122
2421:11841986
2413:17092455
2276:24239827
2268:11673581
2215:23653281
2207:11921051
2048:21820099
1999:22073189
1959:PLOS ONE
1940:15588329
1887:30 April
1861:11791207
1809:storage.
1803:protease
1777:12082556
1742:17565660
1688:(OMIM):
1617:16303764
1576:21549341
1527:(OMIM):
1504:15965709
1444:12189165
1400:11971870
1365:12414822
1309:16571600
1207:12134079
1158:15240430
1039:20301601
878:Cellcept
786:Cystagon
771:cysteine
733:battenin
729:ortholog
611:residues
562:Nonsense
228:seizures
147:Genetics
133:probands
97:proteins
2844:D009472
2769:4698309
2699:4174985
2671:Bibcode
2604:8864279
2378:7668318
2343:1609834
2122:May 30,
2039:3155175
1990:3208569
1967:Bibcode
1733:1906764
1673:9097964
1567:3146726
1512:9916771
1356:1735024
1263:8895569
1111:8160780
1102:1887237
917:History
850:Toronto
602:by the
395:(AR),
260:enzymes
3066:type C
2868:001613
2767:
2732:
2697:
2689:
2663:Nature
2646:
2610:
2602:
2507:
2470:synd/7
2454:
2419:
2411:
2376:
2341:
2274:
2266:
2213:
2205:
2046:
2036:
1997:
1987:
1938:
1931:539297
1928:
1914:: 57.
1859:
1852:384912
1849:
1783:
1775:
1740:
1730:
1716:: 22.
1671:
1615:
1574:
1564:
1529:256730
1510:
1502:
1442:
1398:
1363:
1353:
1307:
1261:
1254:452268
1251:
1205:
1198:117323
1195:
1156:
1109:
1099:
1037:
766:DNAJC5
531:116840
512:609055
505:Type 9
494:600143
487:Type 8
476:610003
466:Type 8
455:610951
448:Type 7
437:601780
430:Type 6
419:256731
412:Type 5
406:DNAJC5
397:162350
393:204300
379:Type 4
368:204200
354:Type 3
343:204500
337:ataxia
325:Type 2
314:256730
296:Type 1
212:rectal
204:muscle
109:spleen
68:
3188:Other
3085:From
3040:From
3017:From
2968:From
2833:330.1
2818:E75.4
2695:S2CID
2608:S2CID
2417:S2CID
2272:S2CID
2211:S2CID
1781:S2CID
1508:S2CID
1136:Brain
880:, an
726:CLN3
679:amine
469:CLN8
460:MFSD8
291:Gene
267:Types
105:liver
101:lipid
2957:(to
2839:MeSH
2828:9-CM
2765:PMID
2730:PMID
2687:PMID
2644:PMID
2600:PMID
2505:PMID
2452:PMID
2440:1762
2409:PMID
2374:PMID
2339:PMID
2264:PMID
2203:PMID
2172:2011
2151:2011
2124:2008
2073:2011
2044:PMID
1995:PMID
1936:PMID
1889:2017
1857:PMID
1825:CLN6
1785:5973
1773:PMID
1738:PMID
1669:PMID
1613:PMID
1572:PMID
1500:PMID
1469:2019
1440:PMID
1396:PMID
1361:PMID
1305:PMID
1259:PMID
1203:PMID
1154:PMID
1107:PMID
1066:help
1046:2016
1035:PMID
722:CLN3
714:CLN3
675:TPP1
667:CLN2
627:PPT
587:The
570:CLN1
564:and
536:CTSD
499:CLN8
481:CLN8
451:CLN7
442:CLN6
424:CLN5
403:CLN6
399:(AD)
373:CLN3
348:TPP1
319:PPT1
287:OMIM
280:Type
237:and
200:skin
162:CLN3
157:gene
3161:NCL
3133:To
2939:of
2890:216
2824:ICD
2809:ICD
2757:doi
2722:doi
2679:doi
2667:188
2592:doi
2555:doi
2501:124
2473:at
2444:doi
2401:doi
2366:doi
2331:doi
2256:doi
2195:doi
2034:PMC
2026:doi
1985:PMC
1975:doi
1926:PMC
1916:doi
1847:PMC
1839:doi
1765:doi
1728:PMC
1718:doi
1659:doi
1603:doi
1599:281
1562:PMC
1554:doi
1492:doi
1430:doi
1388:doi
1351:PMC
1343:doi
1295:doi
1249:PMC
1241:doi
1193:PMC
1185:doi
1144:doi
1140:127
1097:PMC
1093:144
665:The
639:PPT
635:PPT
631:PPT
30:NCL
3231::
3145::
3123::
3109::
3074::
3052::
3029::
2986::
2935::
2888::
2877::
2866::
2842::
2831::
2816::
2813:10
2763:.
2753:18
2751:.
2728:.
2716:.
2693:.
2685:.
2677:.
2665:.
2638:.
2606:.
2598:.
2586:.
2551:18
2549:.
2545:.
2528:23
2526:.
2450:.
2438:.
2415:.
2407:.
2397:21
2395:.
2372:.
2362:57
2360:.
2337:.
2327:42
2325:.
2270:.
2262:.
2252:57
2250:.
2246:.
2209:.
2201:.
2191:51
2189:.
2132:^
2115:.
2056:^
2042:.
2032:.
2022:89
2020:.
2016:.
1993:.
1983:.
1973:.
1961:.
1957:.
1934:.
1924:.
1910:.
1906:.
1880:.
1869:^
1855:.
1845:.
1835:70
1833:.
1829:.
1787:.
1779:.
1771:.
1759:.
1736:.
1726:.
1712:.
1708:.
1696:^
1667:.
1653:.
1649:.
1637:^
1611:.
1597:.
1593:.
1570:.
1560:.
1550:88
1548:.
1544:.
1506:.
1498:.
1486:.
1460:.
1438:.
1426:11
1424:.
1420:.
1408:^
1394:.
1384:11
1382:.
1359:.
1349:.
1339:39
1337:.
1333:.
1321:^
1311:.
1303:.
1291:15
1289:.
1285:.
1271:^
1257:.
1247:.
1237:15
1235:.
1231:.
1215:^
1201:.
1191:.
1181:13
1179:.
1175:.
1152:.
1138:.
1134:.
1122:^
1113:.
1105:.
1091:.
1087:.
1075:^
1058::
1056:}}
1052:{{
1029:.
1014:^
999:.
852:.
802:A
760:.
737:pH
657:.
210:,
206:,
202:,
111:,
107:,
3210:)
3206:/
3202:(
3099:)
3090:(
3068:)
3059:(
3009:)
2995:(
2977:)
2973:(
2961:)
2947:)
2943:(
2925:e
2918:t
2911:v
2826:-
2811:-
2801:D
2771:.
2759::
2736:.
2724::
2718:9
2701:.
2681::
2673::
2650:.
2640:8
2614:.
2594::
2588:6
2561:.
2557::
2511:.
2458:.
2446::
2423:.
2403::
2380:.
2368::
2345:.
2333::
2278:.
2258::
2217:.
2197::
2174:.
2153:.
2126:.
2100:.
2075:.
2050:.
2028::
2001:.
1977::
1969::
1963:6
1942:.
1918::
1912:5
1891:.
1863:.
1841::
1767::
1761:7
1744:.
1720::
1714:8
1675:.
1661::
1655:6
1619:.
1605::
1578:.
1556::
1514:.
1494::
1488:6
1471:.
1446:.
1432::
1402:.
1390::
1367:.
1345::
1297::
1265:.
1243::
1209:.
1187::
1160:.
1146::
1068:)
1048:.
673:(
385:(
360:(
331:(
302:(
230:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
