Beta thalassemia - Knowledge

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genes that could give rise to offspring with sickle cell disease. Patients diagnosed with beta thalassemia have MCH ≤ 26 pg and an RDW < 19. Of 10,148 patients, 1,739 patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia. This screening procedure proved insensitive in populations of West African ancestry because of the indicators has high prevalence of alpha thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples. Screening has shown reduced incidence; by 1995 the prevalence in Italy reduced from 1:250 to 1:4000, and a 95% decrease in that region. The decrease in incidence has benefitted those affected with thalassemia, as the demand for blood has decreased, therefore improving the supply of treatment.

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packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patient's antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote normal growth and physical activities, and suppress bone marrow hyperactivity and extramedullary hematopoiesis, helping shrink painful masses in some cases. However, these benefits must be weighed against considerations of iron overload, and adjustments should be made as the clinical course progresses.

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morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells. Patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. The different surgical techniques are the open and laparoscopic method. The laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. Those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least one week (preferably three weeks) before the surgery.

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beta-thalassemia carrier state (beta thalassemia minor) conferring a resistance to malaria. In the United States, thalassemia's prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23, with only 1% of consultants being older than 75, and 69% being 15–59. It is estimated that 1.5% of the world's population are carriers and 40,000 affected infants are born with the disease annually. Beta thalassemia major is usually fatal in infancy if blood transfusions are not initiated immediately.

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induce oxygen species and is responsible for cellular damage. The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. Iron chelation is a medical therapy that may prevent the complications of iron overload. Every unit of transfused blood contains 200–250 mg of iron and the body has no natural mechanism to remove excess iron. The excess iron can be removed by iron chelators (deferoxamine, deferiprone and deferasirox). Liver iron concentration (LIC) can be measured by R2 or T2*

672:(the storage form of iron) is routinely measured in those with beta thalassemia to determine the degree of iron overload; with increased ferritin levels directing the use of iron chelation therapy. The three iron chelators; subcutaneous deferoxamine, oral deferiprone and oral deferasirox can be used as monotherapy or in combination, they have all been shown to decrease serum/systemic iron levels, hepatic and cardiac iron levels as well as decreasing the risk of cardiac arrhythmia, heart failure and death. Hepatic and myocardial 233:. Heart failure, growth impairment, diabetes and osteoporosis are life-threatening conditions which can be caused by beta thalassemia major. The main cardiac abnormalities seen as a result of beta thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathy, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia, and increased 618: 404: 2831: 51: 3653: 2827: 2883: 480: 173: 451:

iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits. Thalassemias typically affect only the mRNAs for production of the beta chains (hence the name). Since the mutation may be a change in only a single base (

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All beta thalassemias may exhibit abnormal red blood cells; a family history is followed by DNA analysis. This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in

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Additional symptoms of beta thalassemia major or intermedia include the classic symptoms of moderate to severe anemia including fatigue, growth and developmental delay in childhood, leg ulcers and organ failure. Ineffective erythropoiesis (red blood cell production) can also lead to compensatory bone

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signaling, thus enhancing erythroid maturation. The medication has been shown to reduce the transfusion burden by 33% in adults with transfusion dependent beta thalassemia as compared to placebo and was also associated with decreased ferritin levels (with no significant decreases in liver or cardiac

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Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9–10.5 g/dL (11–12 g/dL in those with concomitant heart disease). To ensure quality blood transfusions, the

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have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of

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inheritance of a beta-thalassemia mutation and patients usually have microcytosis with borderline hypochromic anemia and they are usually asymptomatic or have mild symptoms. Beta thalassemia minor can also present as beta thalassemia silent carriers; those who inherit a beta thalassemic mutation but

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The disorder is more prevalent in certain ethnicities and age groups. Beta thalassemia is most prevalent in the "thalassemia belt" which includes areas in Sub-Saharan Africa, the Mediterranean extending into the Middle East and Southeast Asia. This geographical distribution is thought to be due to

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Patients with beta thalassemia intermedia typically present at >2 years of age with mild-to-moderate anemia (7-10 g/dL). They may require no transfusions or may require episodic blood transfusions during certain circumstances (infection, pregnancy, surgery). Patients with frequent transfusions

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For management decisions and clinical trial eligibility, the categories of transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) are used. Patients are usually considered as having NTDT if they have received fewer than 6 red blood cell units in the past 6 months

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During normal iron homeostasis the circulating iron is bound to transferrin. But with iron overload (such as with frequent blood transfusions), the ability for transferrin to bind iron is exceeded and non-transferrin bound iron accumulated. This unbound iron is toxic due to its high propensity to

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Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin. A study aimed at detecting the

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Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on family history, if a person's parents or grandparents had beta thalassemia major or intermedia, there is a 75% (3 out of 4) probability (see inheritance chart at top of page) of the mutated gene being

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other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include

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portions of the DNA template. Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoglobin's normal alpha and beta subunits each have an

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Nondeletion forms: These defects, in general, involve a single base substitution or small insertions near or upstream of the β globin gene. Most often, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the

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Three main forms have been described: thalassemia minor, thalassemia intermedia, and thalassemia major which vary from asymptomatic or mild symptoms to severe anemia requiring lifelong transfusions. Individuals with beta thalassemia major (those who are homozygous for thalassemia mutations, or

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Patients with thalassemia major are more inclined to have a splenectomy. The use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Splenectomy is also associated with increased risk of infections and increased

3360: 2904: 762:. Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in 637:. Iron chelation treatment is necessary to prevent damage to internal organs in cases of iron overload. Advances in iron chelation treatments allow patients with thalassemia major to live long lives with access to proper treatment. Popular chelators include 652:

was approved for use in 2005 in some countries. Bone marrow transplantation is the only cure and is indicated for patients with severe thalassemia major. Transplantation can eliminate a patient's dependence on transfusions. Absent a matching donor, a

253:(enlargement of the liver and spleen). Other tissues in the body can also become sites of erythropoiesis, leading to extramedullary hematopoietic pseudotumors which may cause compressive symptoms if they occur in the thoracic cavity or spinal canal. 2828:"Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia" 140:

to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

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are major clinical manifestations. However, diagnosing thalassemia from symptoms alone is inadequate. Physicians note these signs as associative due to this disease's complexity. The following associative signs can attest to the severity of the

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marrow expansion which can then lead to bony changes/deformities, bone pain and craniofacial abnormalities. Extramedullary organs such as the liver and spleen that can also undergo erythropoiesis become activated leading to

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inheriting 2 mutations) usually present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by

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inherited by an offspring. Even if a child does not have beta thalassemia major or intermedia, they can still be a carrier, possibly resulting in future generations of their offspring having beta thalassemia.

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Beta thalassemia genetics, the picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent).

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In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the

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Peripheral blood smear from a person with beta thalassemia. The red blood cells vary greatly in shape and size and some look empty because of their low hemoglobin content (Giemsa stain).

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for the beta thalassemia mutation) usually present later in life with mild to moderate symptoms of anemia. Beta thalassemia trait (also known as beta thalassemia minor) involves

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Sabloff, Mitchell; Chandy, Mammen; Wang, Zhiwei; Logan, Brent R.; Ghavamzadeh, Ardeshir; Li, Chi-Kong; Irfan, Syed Mohammad; Bredeson, Christopher N.; Cowan, Morton J. (2011).

811:(ACE-536) is a recombinant fusion protein that is used as a treatment in adults with transfusion dependent beta thalassemia. It consists of a modified extra-cellular domain of 282:

Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if they allow some β globin chain formation to occur.

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Affected individuals can often manage a normal life but may need occasional transfusions, e.g., at times of illness or pregnancy, depending on the severity of their anemia.

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Patients with beta thalassemia minor are usually asymptomatic and are often monitored without treatment. Beta thalassemia minor may coexist with other conditions such as

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The treatment was approved in the United Kingdom for the treatment of transfusion-dependent beta thalassemia in November 2023 and in the United States in January 2024.

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can be used as an alternative. In patients with iron overload, it is reasonable to start chelation therapy if LIC is >5 mg Fe per gram dry weight (dw) or serum

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Beta thalassemia is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases, an inherited mutation damages the assembly of the

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Another risk factor is ancestry. Beta thalassemia occurs most often in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry.

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Basic Genetics: A Primer Covering Molecular Composition of Genetic Material, Gene Expression and Genetic Engineering, and Mutations and Human Genetic

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bound to the Fc portion of the human IgG1 antibody. The molecule binds to select transforming growth factor beta superfamily ligands to block

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is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a

4013: 3574: 2901:"Vertex and CRISPR Therapeutics Announce US FDA Approval of Casgevy (exagamglogene autotemcel) for the Treatment of Sickle Cell Disease" 2362:

Greer, John P.; Arber, Daniel A.; Glader, Bertil; List, Alan F.; Means, Robert T.; Paraskevas, Frixos; Rodgers, George M. (2013-08-29).

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Greer, John P.; Arber, Daniel A.; Glader, Bertil; List, Alan F.; Means, Robert T.; Paraskevas, Frixos; Rodgers, George M. (2013-08-29).

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have no hematologic abnormalities nor symptoms. Some people with thalassemia are susceptible to health complications that involve the

3003: 373:: Occurs when both alleles have thalassemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia, 4022: 3993: 3390: 3261: 1419: 1110: 874: 658: 3925: 1598: 560:; and serum bilirubin. The expected pattern on hemoglobin electrophoresis in people with beta-thalassemia is an increased level of 4053: 1457: 520:, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a 2805: 2654: 805:

level is >800 ng/mL. Chelation therapy may be discontinued when LIC <3 mg Fe per gram dw or serum ferritin <300 ng/mL.

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Priti; Gallagher, Patrick G.; Braddock, Demetrios T.; Saltzman, W. Mark; Ly, Danith H.; Glazer, Peter M. (26 October 2016).

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that, when combined or co-existing, may cause a person to have iron overload of the liver and more severe liver disease.

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Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (β) or

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is also used to quantify the iron deposition in target organs, especially the heart and liver, to guide therapy.

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from peripheral hemolysis). These complications are mostly found in thalassemia major and intermedia patients.

3472:"In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery" 2041: 1494:

Barton, James C.; Edwards, Corwin Q.; Phatak, Pradyumna D.; Britton, Robert S.; Bacon, Bruce R. (2010-07-22).

2532:"From debilitating illness to a 'normal' life, new gene therapy treatment promises to transform rare disease" 4125: 3976: 3668: 2092:

Orkin, Stuart H.; Nathan, David G.; Ginsburg, David; Look, A. Thomas; Fisher, David E.; Lux, Samuel (2009).

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McKinney, Emily Slone; James, Susan R.; Murray, Sharon Smith; Nelson, Kristine; Ashwill, Jean (2014-04-17).

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can be curative for some children. Patients receive frequent blood transfusions that lead to or potentiate

4232: 4116: 3777: 2117: 1000: 846: 727: 549: 521: 185:; therefore, prenatal screening is very important. Those with beta thalassemia intermedia (those who are 4096: 3863: 3636: 2593:"UPDATED: Bluebird bio's $ 2.8M gene therapy Zynteglo wins FDA backing. Will its US launch take flight?" 928: 568:. The diagnosis is confirmed with hemoglobin electrophoresis or high performance liquid chromatography. 2233:

Gibson F, Mason K, Serjeant B, Kulozik A, Happich M, Tolle G, Hambleton I, Serjeant G (January 2012).

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and severe bone deformities, and progresses to death before age 20. Treatment consists of periodic

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Taher, Ali T.; Musallam, Khaled M.; Cappellini, M. Domenica (25 February 2021). "β-Thalassemias".

4187: 4160: 3765: 3411: 2797: 2646: 1401: 854: 850: 492: 250: 203: 2235:"Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry" 4192: 4182: 4141: 4136: 4131: 4072: 3904: 3893: 3883: 3817: 3800: 3791: 3773: 3735: 3596: 3509: 3457: 3350: 3323: 3297: 3173: 3163: 3121: 3083: 3058: 2789: 2638: 2487: 2438: 2395: 2369: 2331: 2295: 2264: 2215: 2153: 2097: 1991: 1954: 1916: 1878: 1824: 1775: 1717: 1707: 1669: 1631: 1604: 1566: 1539: 1501: 1463: 1425: 1393: 1311: 1263: 1236: 1211: 1142: 1039: 1029: 1003:), thus perpetuating the mutation. In that respect, the various thalassemias resemble another 984: 834: 626: 533: 378: 360: 316: 91: 63: 3873: 3812: 3499: 3491: 3048: 3038: 2781: 2630: 2477: 2469: 2254: 2246: 2205: 2197: 1987:

Beta Thalassemia: New Insights for the Healthcare Professional: 2013 Edition: ScholarlyBrief

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Taeusch, H. William; Ballard, Roberta A.; Gleason, Christine A.; Avery, Mary Ellen (2005).

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Surgically removed spleen of a thalassemic child. It is about 15 times larger than normal.

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Hair-on-end (or "crew cut") on skull X-ray: new bone formation due to the inner table.

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form: Only one of β globin alleles bears a mutation. Affected individuals will develop

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Hydroxamic Acids: Advances in Research and Application: 2011 Edition: ScholarlyPaper

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The hand of a person with severe anemia (left, wearing ring) compared to one without

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The body's inability to construct new beta-chains leads to the underproduction of

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approve a gene therapy treatment for use with beta thalassemia. The manufacturer

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stretches of DNA that play important roles in regulating produced protein levels

382: 242: 125: 3199: 2785: 2676:"Sickle cell: 'The revolutionary gene-editing treatment that gave me new life'" 2634: 50: 3847: 3677: 3601: 3553: 3447: 3385:. In Lichtman, MA; Kipps, TJ; Seligsohn, U; Kaushansky, K; Prchal, JT (eds.). 3043: 2957: 2857:"FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease" 2250: 557: 496: 428: 420: 133: 68: 2283: 2186:"Carrier screening for Beta-thalassaemia: a review of international practice" 1842: 1761: 1721: 3620: 3412:"Thalassemia: Genetic Blood Disorder Expected To Double In Next Few Decades" 964: 932: 501: 210: 199: 153: 3513: 3461: 3062: 2793: 2675: 2642: 2491: 2442: 2299: 2268: 2219: 1828: 1779: 1397: 1315: 1215: 1196: 983:

are carriers of beta-thalassaemia genes, while 10% of the population carry

148:(adult hemoglobin). The imbalance of alpha to beta globin chains leads to 3177: 2437:. National Institute of Diabetes and Digestive and Kidney Diseases. 2018. 1389: 3631: 2458:"HLA-matched sibling bone marrow transplantation for β-thalassemia major" 2435:

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury

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peoples and this geographical association is responsible for its naming:

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for the treatment of transfusion-dependent beta thalassemia developed by

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Cousens, N. E.; Gaff, C. L.; Metcalfe, S. A.; Delatycki, M. B. (2010).

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Pathophysiology: The Biologic Basis for Disease in Adults and Children

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charges $ 2.8 million in the United States for its one-time treatment

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Vasudevan, D. M.; Sreekumari, S.; Vaidyanathan, Kannan (2011-11-01).

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On June 10, 2022, a U.S. federal advisory panel recommended that the

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for splenomegaly and chelation of transfusion-related iron overload.

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Guidelines for the Management of Transfusion Dependent Thalassaemia

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This article incorporates text from this source, which is in the

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Diagnostic Molecular Pathology in Practice: A Case-Based Approach

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The beta form of thalassemia is particularly prevalent among the

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The thalassemia trait may confer a degree of protection against

592: 447: 424: 3681: 2118:"What Are the Signs and Symptoms of Thalassemias? — NHLBI, NIH" 571:

Skeletal changes associated with expansion of the bone marrow:

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Introduction to Pathology for the Physical Therapist Assistant

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Protein HBB PDB 1a00. This is a healthy beta globin protein.

217:) causes serious complications within the liver, heart, and 2830:(Press release). Vertex Pharmaceuticals. 16 November 2023. 2903:(Press release). Vertex Pharmaceuticals. 8 December 2023. 919:, the highest concentrations of the disease are found in 743:

is the first cell-based gene therapy treatment utilizing

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Guidelines for the Clinical Management of Thalassaemia

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Surgical Treatment: Evidence-Based and Problem-Oriented

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Anderson, Gregory J.; McLaren, Gordon D. (2012-01-16).

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Nathan and Oski's Hematology of Infancy and Childhood

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Contemporary Internal Medicine: Clinical Case Studies

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that result in variable outcomes ranging from severe

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Bowen, Juan M.; Mazzaferri, Ernest L. (2012-12-06).

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Two major groups of mutations can be distinguished:

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Medicines and Healthcare products Regulatory Agency

2079:, Imperial College of London Department of Medicine 1744:Saliba AN, Musallam KM, Taher AT (September 2023). 1662:Barton, James C.; Edwards, Corwin Q. (2000-01-13). 1532:McCance, Kathryn L.; Huether, Sue E. (2013-12-13). 100: 90: 82: 74: 62: 40: 35: 2851: 2849: 1624:Disorders, National Organization for Rare (2003). 1178:Galanello, Renzo; Origa, Raffaella (21 May 2010). 3383:"The Thalassemias: Disorders of Globin Synthesis" 595:should routine electrophoresis prove difficult. 2282:Muncie, Herbert L.; Campbell, James S. (2009). 1232:Goldman-Cecil Medicine: Expert Consult — Online 1229:Goldman, Lee; Schafer, Andrew I. (2015-04-21). 504:: pallor, poor growth, inadequate food intake, 319:. Detection usually involves lower than normal 3343:Abouelmagd, Ahmed; Ageely, Hussein M. (2013). 3290:Berg, Sheri; Bittner, Edward A. (2013-10-16). 2042:"How Are Thalassemias Diagnosed? — NHLBI, NIH" 3693: 2623:"CRISPR's "magnificent moment" in the clinic" 1459:Iron Physiology and Pathophysiology in Humans 1173: 1171: 1169: 1103:"Beta Thalassemia Treatment & Management" 237:destruction by the spleen due to ineffective 128:caused by reduced or absent synthesis of the 8: 3842:Glucose-6-phosphate dehydrogenase deficiency 1912:Textbook of Biochemistry for Dental Students 1874:Practical Management of Haemoglobinopathies 706:Gene editing therapies aimed at increasing 625:Affected children require regular lifelong 4198:Hereditary persistence of fetal hemoglobin 3959: 3823: 3761: 3752: 3723: 3700: 3686: 3678: 3527: 2926:Commissioner, Office of the (2024-01-16). 1700:Lippincott Williams & Wilkins (2009). 959:are heavily affected in particular. Other 722:, sold under the brand name Casgevy, is a 710:production in beta thalassemia as well as 276:hereditary persistence of fetal hemoglobin 241:further releases additional iron into the 49: 32: 4223:Disorders of globin and globulin proteins 4150:Mean corpuscular hemoglobin concentration 3972:Warm antibody autoimmune hemolytic anemia 3503: 3389:(8 ed.). The McGraw-Hill Companies. 3052: 3042: 3031:Therapeutics and Clinical Risk Management 2958:"Splenectomy for hematological disorders" 2481: 2258: 2209: 1818: 1793:Ward, Amanda J; Cooper, Thomas A (2009). 1769: 1739: 1737: 1735: 1733: 1731: 1424:. Jones & Bartlett Publishers. 2011. 1205: 1195: 78:Thalassemia minor, intermediate and major 3293:The MGH Review of Critical Care Medicine 2096:(7th ed.). Philadelphia: Saunders. 2087: 2085: 1562:Molecular Pathology in Clinical Practice 1371: 1369: 1367: 1365: 1363: 1361: 1359: 1357: 1355: 1353: 1351: 1349: 1347: 1345: 495:and right-upper quadrant pain caused by 284: 3446:Cao, Antonio; Galanello, Renzo (2010). 2960:. In Holzheimer RG, Mannick JA (eds.). 1343: 1341: 1339: 1337: 1335: 1333: 1331: 1329: 1327: 1325: 1056: 1064: 1062: 1060: 423:. DNA contains both the instructions ( 3456:. University of Washington, Seattle. 3296:. Lippincott Williams & Wilkins. 3082:. Lippincott Williams & Wilkins. 2834:from the original on 22 November 2023 2749:from the original on 25 November 2023 2368:. Lippincott Williams & Wilkins. 2330:. Lippincott Williams & Wilkins. 2022:from the original on 20 November 2016 1706:. Lippincott Williams & Wilkins. 1630:. Lippincott Williams & Wilkins. 1259:Oxford Handbook of Clinical Pathology 1130: 1128: 7: 3859:triosephosphate isomerase deficiency 2907:from the original on 9 December 2023 2871:from the original on 8 December 2023 2808:from the original on 4 December 2023 2716:from the original on 4 December 2023 747:technology to be approved by the US 395:and none in the preceding 2 months. 4014:paroxysmal nocturnal hemoglobinuria 3982:Donath–Landsteiner hemolytic anemia 3025:Cappellini, Maria Domenica (2007). 2745:(Press release). 16 November 2023. 1559:Leonard, Debra G. B. (2007-11-25). 1497:Handbook of Iron Overload Disorders 2591:Kansteiner, Fraiser (2022-08-17). 2542:from the original on 28 April 2024 2190:European Journal of Human Genetics 915:) is the Greek word for blood. In 760:hematopoietic stem cell transplant 25: 4023:Microangiopathic hemolytic anemia 3994:Mixed autoimmune hemolytic anemia 3422:from the original on 4 April 2017 3152:Brissot P, Cappellini MD (2014). 3006:from the original on 4 April 2017 2394:. ScholarlyEditions. 2012-01-09. 1990:. ScholarlyEditions. 2013-07-22. 1113:from the original on 4 April 2017 875:non-alcoholic fatty liver disease 659:preimplantation genetic diagnosis 4054:Hemolytic disease of the newborn 3651: 2881: 459:to make that single correction. 3393:from the original on 2013-11-04 3363:from the original on 2023-01-14 3134:from the original on 2023-01-14 3117:Blood and Bone Marrow Pathology 3096:from the original on 2023-01-14 2938:from the original on 2024-01-17 2928:"FDA Roundup: January 16, 2024" 2686:from the original on 2023-03-27 2657:from the original on 2023-03-27 2603:from the original on 2023-01-25 2573:from the original on 2023-08-04 2530:Karen Weintraub (14 Jun 2022). 2512:from the original on 2016-03-04 2344:from the original on 2023-01-14 2306:from the original on 2019-12-15 2166:from the original on 2023-01-14 2128:from the original on 2015-05-25 2052:from the original on 2017-07-28 1967:from the original on 2023-01-14 1950:Avery's Diseases of the Newborn 1929:from the original on 2023-01-14 1891:from the original on 2023-01-14 1853:from the original on 2015-05-11 1682:from the original on 2023-01-14 1644:from the original on 2023-01-14 1579:from the original on 2023-01-14 1514:from the original on 2023-01-14 1476:from the original on 2023-01-14 1438:from the original on 2023-01-14 1378:New England Journal of Medicine 1276:from the original on 2023-01-14 1155:from the original on 2023-01-14 1080:from the original on 2015-05-13 813:human activin receptor type IIB 3987:Paroxysmal cold hemoglobinuria 3079:The 5 Minute Pediatric Consult 2365:Wintrobe's Clinical Hematology 2327:Wintrobe's Clinical Hematology 2146:Schrijver, Iris (2011-09-09). 1871:Okpala, Iheanyi (2008-04-15). 1795:"The pathobiology of splicing" 1703:Professional Guide to Diseases 1668:. Cambridge University Press. 1500:. Cambridge University Press. 453:single-nucleotide polymorphism 1: 3076:Schwartz, M. William (2012). 2996:"Beta Thalassemia Medication" 2561:Myshko, Denise (2022-04-13). 1308:10.1016/S0140-6736(22)00536-0 681:Weill Cornell Medical College 4228:Hereditary hemolytic anemias 3938:Southeast Asian ovalocytosis 3926:Minkowski–Chauffard syndrome 3381:Weatherall, David J (2010). 3120:. Elsevier Health Sciences. 2863:Food and Drug Administration 2768:Sheridan C (November 2023). 2474:10.1182/blood-2010-09-306829 2284:"Alpha and Beta Thalassemia" 1953:. Elsevier Health Sciences. 1627:NORD Guide to Rare Disorders 1538:. Elsevier Health Sciences. 1256:Carton, James (2012-02-16). 1235:. Elsevier Health Sciences. 1141:. Elsevier Health Sciences. 749:Food and Drug Administration 3322:. AuthorHouse. 2013-02-06. 3205:Online Etymology Dictionary 2704:Stein R (31 October 2023). 2621:Zipkin, Mark (2019-12-06). 927:coastal regions. The major 824:Beta thalassemia intermedia 542:total iron-binding capacity 104:Depends on type (see types) 4249: 4047:Drug-induced nonautoimmune 4028:Thrombotic microangiopathy 3854:pyruvate kinase deficiency 3228: 3220: 2983:(2nd ed.). NBK173967. 2915:– via Business Wire. 2842:– via Business Wire. 2786:10.1038/d41587-023-00016-6 2635:10.1038/d41587-019-00035-2 795:magnetic resonance imaging 718:gene have been developed. 530:hemoglobin electrophoresis 221:. Severe symptoms include 150:ineffective erythropoiesis 4033:Hemolytic–uremic syndrome 3945:Hereditary stomatocytosis 3933:Hereditary elliptocytosis 3044:10.2147/tcrm.2007.3.2.291 2956:Uranüs S, Sill H (2001). 2288:American Family Physician 2251:10.1007/s12687-011-0069-6 1877:. John Wiley & Sons. 512:, maxillary hyperplasia, 455:), on-going efforts seek 86:Mutations in the HBB gene 57: 48: 3921:Hereditary spherocytosis 3349:. Universal-Publishers. 1799:The Journal of Pathology 1762:10.1182/blood.2023020683 871:chronic hepatitis C 867:chronic hepatitis B 764:exagamglogene autotemcel 745:CRISPR/Cas9 gene editing 741:Exagamglogene autotemcel 720:Exagamglogene autotemcel 701:betibeglogene autotemcel 323:value (<80 fL). 229:, and in extreme cases, 4126:Mean corpuscular volume 4090:Diamond–Blackfan anemia 4042:Drug-induced autoimmune 3977:Cold agglutinin disease 3783:Plummer–Vinson syndrome 3244:A Greek–English Lexicon 1843:"the definition of dna" 1074:Genetics Home Reference 991:Evolutionary adaptation 879:alcoholic liver disease 663:human leukocyte antigen 631:Bone marrow transplants 564:and slightly increased 321:mean corpuscular volume 44:Microcytemia, beta type 3778:Iron-deficiency anemia 1197:10.1186/1750-1172-5-11 1138:Maternal-Child Nursing 1007:affecting hemoglobin, 1001:heterozygous advantage 861:Beta thalassemia minor 847:compound heterozygotes 728:Vertex Pharmaceuticals 622: 613:Beta thalassemia major 550:peripheral blood smear 524:. These tests include 522:differential diagnosis 487:Abdominal pain due to 484: 408: 335:Thalassemia intermedia 187:compound heterozygotes 177: 18:Beta-thalassemia major 4097:Pure red cell aplasia 3864:hexokinase deficiency 3476:Nature Communications 3319:Haematology Made Easy 3235:Liddell, Henry George 1390:10.1056/NEJMra2021838 961:Mediterranean peoples 929:Mediterranean islands 684:β-globin production. 620: 482: 406: 175: 4102:Sideroblastic anemia 3910:Hemoglobin C disease 3796:Megaloblastic anemia 2774:Nature Biotechnology 2627:Nature Biotechnology 2202:10.1038/ejhg.2010.90 849:have been reported. 841:; however, dominant 657:can be conceived by 526:complete blood count 198:(hypersplenism) and 124:. They are forms of 3901:Sickle cell disease 3496:10.1038/ncomms13304 3488:2016NatCo...713304B 3387:Williams Hematology 3272:on October 30, 2011 2867:. 8 December 2023. 1184:Orphanet J Rare Dis 1035:Anisopoikilocytosis 1009:sickle-cell disease 853:is recommended and 839:autosomal recessive 732:CRISPR Therapeutics 556:, or target cells; 514:dental malocclusion 4188:Sulfhemoglobinemia 3612:External resources 3448:"Beta-Thalassemia" 2075:2015-09-28 at the 1915:. JP Medical Ltd. 1302:(10343): 2310–24. 1180:"Beta-thalassemia" 1070:"Beta thalassemia" 985:alpha-thalassaemia 855:prenatal diagnosis 851:Genetic counseling 837:. Transmission is 714:by inhibiting the 712:sickle cell anemia 648:The oral chelator 627:blood transfusions 623: 562:hemoglobin A2 493:splenic infarction 485: 413:messenger-type RNA 409: 251:hepatosplenomegaly 209:Excess iron (from 204:hyperbilirubinemia 178: 168:Signs and symptoms 4210: 4209: 4206: 4205: 4193:Reticulocytopenia 4183:Methemoglobinemia 4171: 4170: 4062: 4061: 4002: 4001: 3801:Pernicious anemia 3744: 3743: 3736:Polycythemia vera 3646: 3645: 3356:978-1-61233-192-8 3329:978-1-4772-4651-1 3303:978-1-4511-7368-0 3198:Harper, Douglas. 3169:978-9963-717-06-4 3127:978-0-7020-4535-6 3089:978-1-4511-1656-4 2401:978-1-4649-5208-1 2375:978-1-4698-4622-4 2337:978-1-4698-4622-4 2239:J Community Genet 2159:978-3-642-19677-5 2122:www.nhlbi.nih.gov 2103:978-1-4160-3430-8 2046:www.nhlbi.nih.gov 1997:978-1-4816-6347-2 1960:978-0-7216-9347-7 1922:978-93-5025-488-2 1884:978-1-4051-4020-1 1811:10.1002/path.2649 1713:978-0-7817-7899-2 1675:978-0-521-59380-9 1637:978-0-7817-3063-1 1610:978-1-4615-6713-4 1572:978-0-387-33227-7 1545:978-0-323-08854-1 1507:978-1-139-48939-3 1469:978-1-60327-484-5 1431:978-0-7637-9908-3 1269:978-0-19-162993-8 1242:978-0-323-32285-0 1148:978-0-323-29377-8 1040:Delta-thalassemia 1030:Alpha-thalassemia 907:word for sea and 835:chelation therapy 566:hemoglobin F 552:, which may show 534:serum transferrin 392: 391: 379:blood transfusion 355:Thalassemia major 317:microcytic anemia 304:Thalassemia minor 117:) are a group of 111:Beta thalassemias 108: 107: 92:Diagnostic method 30:Medical condition 16:(Redirected from 4240: 3960: 3874:hemoglobinopathy 3824: 3762: 3753: 3724: 3702: 3695: 3688: 3679: 3669:Beta thalassemia 3655: 3654: 3528: 3517: 3507: 3465: 3432: 3431: 3429: 3427: 3408: 3402: 3401: 3399: 3398: 3378: 3372: 3371: 3369: 3368: 3340: 3334: 3333: 3314: 3308: 3307: 3287: 3281: 3280: 3278: 3277: 3268:. Archived from 3258: 3252: 3231: 3230: 3223: 3222: 3216: 3210: 3209: 3195: 3189: 3188: 3186: 3185: 3149: 3143: 3142: 3140: 3139: 3111: 3105: 3104: 3102: 3101: 3073: 3067: 3066: 3056: 3046: 3022: 3016: 3015: 3013: 3011: 2991: 2985: 2984: 2972: 2966: 2965: 2953: 2947: 2946: 2944: 2943: 2923: 2917: 2916: 2914: 2912: 2897: 2891: 2885: 2884: 2880: 2878: 2876: 2853: 2844: 2843: 2841: 2839: 2824: 2818: 2817: 2815: 2813: 2765: 2759: 2758: 2756: 2754: 2732: 2726: 2725: 2723: 2721: 2701: 2695: 2694: 2692: 2691: 2672: 2666: 2665: 2663: 2662: 2618: 2612: 2611: 2609: 2608: 2588: 2582: 2581: 2579: 2578: 2558: 2552: 2551: 2549: 2547: 2527: 2521: 2520: 2518: 2517: 2502: 2496: 2495: 2485: 2453: 2447: 2446: 2427: 2421: 2412: 2406: 2405: 2386: 2380: 2379: 2359: 2353: 2352: 2350: 2349: 2321: 2315: 2314: 2312: 2311: 2279: 2273: 2272: 2262: 2230: 2224: 2223: 2213: 2181: 2175: 2174: 2172: 2171: 2143: 2137: 2136: 2134: 2133: 2114: 2108: 2107: 2089: 2080: 2067: 2061: 2060: 2058: 2057: 2038: 2032: 2031: 2029: 2027: 2008: 2002: 2001: 1982: 1976: 1975: 1973: 1972: 1944: 1938: 1937: 1935: 1934: 1906: 1900: 1899: 1897: 1896: 1868: 1862: 1861: 1859: 1858: 1839: 1833: 1832: 1822: 1790: 1784: 1783: 1773: 1741: 1726: 1725: 1697: 1691: 1690: 1688: 1687: 1659: 1653: 1652: 1650: 1649: 1621: 1615: 1614: 1594: 1588: 1587: 1585: 1584: 1556: 1550: 1549: 1529: 1523: 1522: 1520: 1519: 1491: 1485: 1484: 1482: 1481: 1453: 1447: 1446: 1444: 1443: 1416: 1410: 1409: 1373: 1320: 1319: 1291: 1285: 1284: 1282: 1281: 1253: 1247: 1246: 1226: 1220: 1219: 1209: 1199: 1175: 1164: 1163: 1161: 1160: 1132: 1123: 1122: 1120: 1118: 1098: 1089: 1088: 1086: 1085: 1066: 1045:Hemoglobinopathy 1005:genetic disorder 981:Turkish Cypriots 857:may be offered. 708:fetal hemoglobin 548:and urobilogen; 427:) for stringing 357: 356: 337: 336: 306: 305: 285: 219:endocrine glands 158:iron homeostasis 53: 36:Beta-thalassemia 33: 21: 4248: 4247: 4243: 4242: 4241: 4239: 4238: 4237: 4213: 4212: 4211: 4202: 4167: 4111: 4070: 4058: 3998: 3949: 3815: 3807: 3740: 3715: 3713:red blood cells 3706: 3676: 3675: 3674: 3656: 3652: 3647: 3642: 3641: 3607: 3606: 3539: 3525: 3520: 3468: 3445: 3441: 3439:Further reading 3436: 3435: 3425: 3423: 3410: 3409: 3405: 3396: 3394: 3380: 3379: 3375: 3366: 3364: 3357: 3342: 3341: 3337: 3330: 3316: 3315: 3311: 3304: 3289: 3288: 3284: 3275: 3273: 3260: 3259: 3255: 3249:Perseus Project 3217: 3213: 3197: 3196: 3192: 3183: 3181: 3170: 3154:"Liver Disease" 3151: 3150: 3146: 3137: 3135: 3128: 3113: 3112: 3108: 3099: 3097: 3090: 3075: 3074: 3070: 3024: 3023: 3019: 3009: 3007: 2994:Advani, Pooja. 2993: 2992: 2988: 2974: 2973: 2969: 2955: 2954: 2950: 2941: 2939: 2925: 2924: 2920: 2910: 2908: 2899: 2898: 2894: 2882: 2874: 2872: 2855: 2854: 2847: 2837: 2835: 2826: 2825: 2821: 2811: 2809: 2767: 2766: 2762: 2752: 2750: 2734: 2733: 2729: 2719: 2717: 2703: 2702: 2698: 2689: 2687: 2674: 2673: 2669: 2660: 2658: 2620: 2619: 2615: 2606: 2604: 2590: 2589: 2585: 2576: 2574: 2560: 2559: 2555: 2545: 2543: 2529: 2528: 2524: 2515: 2513: 2504: 2503: 2499: 2455: 2454: 2450: 2429: 2428: 2424: 2413: 2409: 2402: 2388: 2387: 2383: 2376: 2361: 2360: 2356: 2347: 2345: 2338: 2323: 2322: 2318: 2309: 2307: 2281: 2280: 2276: 2232: 2231: 2227: 2196:(10): 1077–83. 2183: 2182: 2178: 2169: 2167: 2160: 2145: 2144: 2140: 2131: 2129: 2116: 2115: 2111: 2104: 2091: 2090: 2083: 2077:Wayback Machine 2068: 2064: 2055: 2053: 2040: 2039: 2035: 2025: 2023: 2010: 2009: 2005: 1998: 1984: 1983: 1979: 1970: 1968: 1961: 1946: 1945: 1941: 1932: 1930: 1923: 1908: 1907: 1903: 1894: 1892: 1885: 1870: 1869: 1865: 1856: 1854: 1841: 1840: 1836: 1792: 1791: 1787: 1756:(11): 949–960. 1743: 1742: 1729: 1714: 1699: 1698: 1694: 1685: 1683: 1676: 1661: 1660: 1656: 1647: 1645: 1638: 1623: 1622: 1618: 1611: 1596: 1595: 1591: 1582: 1580: 1573: 1558: 1557: 1553: 1546: 1531: 1530: 1526: 1517: 1515: 1508: 1493: 1492: 1488: 1479: 1477: 1470: 1455: 1454: 1450: 1441: 1439: 1432: 1418: 1417: 1413: 1375: 1374: 1323: 1293: 1292: 1288: 1279: 1277: 1270: 1255: 1254: 1250: 1243: 1228: 1227: 1223: 1177: 1176: 1167: 1158: 1156: 1149: 1134: 1133: 1126: 1116: 1114: 1101:Advani, Pooja. 1100: 1099: 1092: 1083: 1081: 1068: 1067: 1058: 1053: 1026: 1017: 993: 887: 863: 826: 790: 781: 772: 615: 610: 601: 588: 576:Chipmunk facies 477: 465: 415:(mRNA) that is 401: 371:Homozygous form 354: 353: 347: 334: 333: 327: 303: 302: 291:Older synonyms 264: 259: 223:liver cirrhosis 170: 156:, and deranged 122:blood disorders 31: 28: 23: 22: 15: 12: 11: 5: 4246: 4244: 4236: 4235: 4230: 4225: 4215: 4214: 4208: 4207: 4204: 4203: 4201: 4200: 4195: 4190: 4185: 4179: 4177: 4173: 4172: 4169: 4168: 4166: 4165: 4164: 4163: 4158: 4146: 4145: 4144: 4139: 4134: 4121: 4119: 4113: 4112: 4110: 4109: 4104: 4099: 4092: 4087: 4085:Fanconi anemia 4078: 4076: 4064: 4063: 4060: 4059: 4057: 4056: 4050: 4049: 4044: 4038: 4037: 4036: 4035: 4025: 4019: 4018: 4017: 4016: 4003: 4000: 3999: 3997: 3996: 3991: 3990: 3989: 3979: 3974: 3968: 3966: 3957: 3951: 3950: 3948: 3947: 3942: 3941: 3940: 3930: 3929: 3928: 3912: 3907: 3898: 3897: 3896: 3891: 3886: 3869: 3868: 3867: 3866: 3861: 3856: 3844: 3832: 3830: 3821: 3809: 3808: 3806: 3805: 3804: 3803: 3788: 3787: 3786: 3785: 3770: 3768: 3759: 3750: 3746: 3745: 3742: 3741: 3739: 3738: 3732: 3730: 3721: 3717: 3716: 3707: 3705: 3704: 3697: 3690: 3682: 3657: 3650: 3649: 3648: 3644: 3643: 3640: 3639: 3628: 3626:article/199534 3616: 3615: 3613: 3609: 3608: 3605: 3604: 3593: 3582: 3571: 3556: 3540: 3535: 3534: 3532: 3531:Classification 3524: 3523:External links 3521: 3519: 3518: 3466: 3442: 3440: 3437: 3434: 3433: 3403: 3373: 3355: 3335: 3328: 3309: 3302: 3282: 3253: 3211: 3190: 3168: 3144: 3126: 3106: 3088: 3068: 3017: 2986: 2967: 2948: 2918: 2892: 2845: 2819: 2760: 2727: 2696: 2682:. 2022-02-20. 2667: 2613: 2583: 2567:Managed Health 2553: 2522: 2508:. 2012-03-28. 2497: 2468:(5): 1745–50. 2448: 2431:"Deferoxamine" 2422: 2407: 2400: 2381: 2374: 2354: 2336: 2316: 2274: 2225: 2176: 2158: 2138: 2109: 2102: 2081: 2062: 2033: 2012:"Risk Factors" 2003: 1996: 1977: 1959: 1939: 1921: 1901: 1883: 1863: 1847:Dictionary.com 1834: 1785: 1727: 1712: 1692: 1674: 1654: 1636: 1616: 1609: 1589: 1571: 1551: 1544: 1524: 1506: 1486: 1468: 1448: 1430: 1411: 1384:(8): 727–743. 1321: 1286: 1268: 1262:. 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