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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*
661:(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
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222:. 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
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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
237:
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
772:
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
182:
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
1008:
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
817:
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
383:
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
781:
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
456:
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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Bahal, Raman; McNeer, Nicole Ali; Quijano, Elias; Liu, Yanfeng; Sulkowski, Parker; Turchick, Audrey; Lu, Yi-Chien; Bhunia, Dinesh C.; Manna, Arunava; Greiner, Dale L.; Brehm, Michael A.; Cheng, Christopher J.; López-Giráldez, Francesc; Ricciardi, Adele; Beloor, Jagadish; Krause, Diane S.; Kumar,
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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
439:
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
259:
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
169:
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
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751:. 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
626:. 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
641:
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
242:(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.
2817:"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"
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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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567:: bossing of the skull, prominent malar eminence, depression of the bridge of the nose, tendency to a slant of the eye, and exposure of the upper teeth due to hypertrophy of the maxillae.
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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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149:. Patients may require repeated blood transfusions throughout life to maintain sufficient hemoglobin levels. Consequently, patients may also develop severe problems associated with
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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).
800:(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
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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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2008:
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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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2314:
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964:, 6% of total population is carrier of Beta-thalassemia due to highest rate of cousin marriages globally. The data indicate that 15% of the
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988:, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as
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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
4035:
2890:"Vertex and CRISPR Therapeutics Announce US FDA Approval of Casgevy (exagamglogene autotemcel) for the Treatment of Sickle Cell Disease"
2351:
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
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362:: Occurs when both alleles have thalassemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia,
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3250:
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549:; and serum bilirubin. The expected pattern on hemoglobin electrophoresis in people with beta-thalassemia is an increased level of
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509:, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a
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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.
2725:"MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia"
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3151:. Zhonghua Nei Ke Za Zhi. Vol. 28 (3rd ed.). Thalassaemia International Federation. pp. 609–11, 637.
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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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952:, as well as those in the vicinity of the Mediterranean, also have high incidence rates, including people from
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from peripheral hemolysis). These complications are mostly found in thalassemia major and intermedia patients.
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3461:"In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery"
2030:
1483:
Barton, James C.; Edwards, Corwin Q.; Phatak, Pradyumna D.; Britton, Robert S.; Bacon, Bruce R. (2010-07-22).
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2521:"From debilitating illness to a 'normal' life, new gene therapy treatment promises to transform rare disease"
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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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3016:"Exjade® (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion"
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can be curative for some children. Patients receive frequent blood transfusions that lead to or potentiate
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174:; therefore, prenatal screening is very important. Those with beta thalassemia intermedia (those who are
3625:
2582:"UPDATED: Bluebird bio's $ 2.8M gene therapy Zynteglo wins FDA backing. Will its US launch take flight?"
557:. The diagnosis is confirmed with hemoglobin electrophoresis or high performance liquid chromatography.
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138:
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Gibson F, Mason K, Serjeant B, Kulozik A, Happich M, Tolle G, Hambleton I, Serjeant G (January 2012).
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3439:. In Pagon, Roberta A; Bird, Thomas D; Dolan, Cynthia R; Stephens, Karen; Adam, Margaret P (eds.).
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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".
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2224:"Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry"
989:
835:
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510:
992:), thus perpetuating the mutation. In that respect, the various thalassemias resemble another
4085:
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917:
1976:
Beta
Thalassemia: New Insights for the Healthcare Professional: 2013 Edition: ScholarlyBrief
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1936:
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.
8:
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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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786:(MRI). In parts of the world where advanced MRI techniques are not available, serum
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349:
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52:
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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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3251:"WHO | Global epidemiology of haemoglobin disorders and derived service indicators"
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2695:"FDA advisers see no roadblocks for gene-editing treatment for sickle cell disease"
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2495:"Gene Therapy Shows Promise for Treating Beta-Thalassemia and Sickle Cell Disease"
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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
301:
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2665:"Sickle cell: 'The revolutionary gene-editing treatment that gave me new life'"
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3374:. In Lichtman, MA; Kipps, TJ; Seligsohn, U; Kaushansky, K; Prchal, JT (eds.).
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2846:"FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease"
2239:
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2175:"Carrier screening for Beta-thalassaemia: a review of international practice"
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3401:"Thalassemia: Genetic Blood Disorder Expected To Double In Next Few Decades"
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are carriers of beta-thalassaemia genes, while 10% of the population carry
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137:(adult hemoglobin). The imbalance of alpha to beta globin chains leads to
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2426:. National Institute of Diabetes and Digestive and Kidney Diseases. 2018.
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3440:
2447:"HLA-matched sibling bone marrow transplantation for β-thalassemia major"
2424:
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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231:
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2552:"ICER Draft Report Finds Beti-Cel is Cost-Effective for Blood Disorder"
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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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3145:. In Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V (eds.).
1898:
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.
199:
188:
142:
2759:"The world's first CRISPR therapy is approved: who will receive it?"
650:(PGD) to be free of the disease as well as to match the recipient's
3620:
3148:
Guidelines for the Management of Transfusion Dependent Thalassaemia
1654:
Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment
1283:
Kattamis A, Kwiatkowski JL, Aydinok Y (June 2022). "Thalassaemia".
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498:
39:
3103:
Porwit, Anna; McCullough, Jeffrey; Erber, Wendy N. (2011-05-27).
2875:
This article incorporates text from this source, which is in the
2407:
2138:
Diagnostic Molecular Pathology in Practice: A Case-Based Approach
1688:
985:
933:
878:
The beta form of thalassemia is particularly prevalent among the
421:
3568:
984:
The thalassemia trait may confer a degree of protection against
3745:
3537:
2107:"What Are the Signs and Symptoms of Thalassemias? — NHLBI, NIH"
1897:
937:
925:
913:
909:
905:
801:
704:
560:
Skeletal changes associated with expansion of the bone marrow:
432:
184:
126:
1410:
Introduction to Pathology for the Physical Therapist Assistant
3216:
3208:
945:
941:
2172:
396:
Protein HBB PDB 1a00. This is a healthy beta globin protein.
206:) causes serious complications within the liver, heart, and
2819:(Press release). Vertex Pharmaceuticals. 16 November 2023.
581:
436:
413:
2892:(Press release). Vertex Pharmaceuticals. 8 December 2023.
2221:
1935:
1482:
1282:
1123:
908:, the highest concentrations of the disease are found in
732:
is the first cell-based gene therapy treatment utilizing
677:
662:
468:
161:
118:
1085:
1083:
2970:
Guidelines for the Clinical Management of Thalassaemia
2951:
Surgical Treatment: Evidence-Based and Problem-Oriented
2080:
1445:
Anderson, Gregory J.; McLaren, Gordon D. (2012-01-16).
1364:
2966:"2. Blood Transfusion Therapy in β-Thalassaemia Major"
2963:
2444:
3457:
3102:
2083:
Nathan and Oski's Hematology of Infancy and Childhood
1735:"How I treat non-transfusion-dependent β-thalassemia"
1589:
Contemporary Internal Medicine: Clinical Case Studies
1080:
125:
that result in variable outcomes ranging from severe
3515:
2350:
2312:
1586:
Bowen, Juan M.; Mazzaferri, Ernest L. (2012-12-06).
255:
Two major groups of mutations can be distinguished:
2964:Cappellini MD, Cohen A, Eleftheriou A, et al.
2730:
Medicines and Healthcare products Regulatory Agency
2068:, Imperial College of London Department of Medicine
1733:Saliba AN, Musallam KM, Taher AT (September 2023).
1732:
1651:Barton, James C.; Edwards, Corwin Q. (2000-01-13).
1521:McCance, Kathryn L.; Huether, Sue E. (2013-12-13).
2840:
2838:
1613:Disorders, National Organization for Rare (2003).
1167:Galanello, Renzo; Origa, Raffaella (21 May 2010).
3372:"The Thalassemias: Disorders of Globin Synthesis"
3140:
4203:
3331:
584:should routine electrophoresis prove difficult.
3696:
2835:
2686:
2518:
2271:Muncie, Herbert L.; Campbell, James S. (2009).
1775:
1585:
1444:
1221:Goldman-Cecil Medicine: Expert Consult — Online
1218:Goldman, Lee; Schafer, Andrew I. (2015-04-21).
493:: pallor, poor growth, inadequate food intake,
308:. Detection usually involves lower than normal
3332:Abouelmagd, Ahmed; Ageely, Hussein M. (2013).
3279:Berg, Sheri; Bittner, Edward A. (2013-10-16).
2270:
2031:"How Are Thalassemias Diagnosed? — NHLBI, NIH"
1520:
1217:
1166:
812:
3682:
2612:"CRISPR's "magnificent moment" in the clinic"
1650:
1448:Iron Physiology and Pathophysiology in Humans
1162:
1160:
1158:
1092:"Beta Thalassemia Treatment & Management"
226:destruction by the spleen due to ineffective
117:caused by reduced or absent synthesis of the
3831:Glucose-6-phosphate dehydrogenase deficiency
3434:
2914:
2264:
1901:Textbook of Biochemistry for Dental Students
3715:
3278:
1863:Practical Management of Haemoglobinopathies
695:Gene editing therapies aimed at increasing
614:Affected children require regular lifelong
4187:Hereditary persistence of fetal hemoglobin
3689:
3675:
3369:
3013:
2944:
2915:Commissioner, Office of the (2024-01-16).
2579:
1781:
1689:Lippincott Williams & Wilkins (2009).
1155:
979:
948:are heavily affected in particular. Other
711:, sold under the brand name Casgevy, is a
699:production in beta thalassemia as well as
265:hereditary persistence of fetal hemoglobin
230:further releases additional iron into the
38:
4212:Disorders of globin and globulin proteins
4139:Mean corpuscular hemoglobin concentration
3961:Warm antibody autoimmune hemolytic anemia
3492:
3378:(8 ed.). The McGraw-Hill Companies.
3041:
3031:
3020:Therapeutics and Clinical Risk Management
2947:"Splenectomy for hematological disorders"
2809:
2470:
2247:
2198:
2134:
1807:
1782:Ward, Amanda J; Cooper, Thomas A (2009).
1758:
1728:
1726:
1724:
1722:
1720:
1612:
1413:. Jones & Bartlett Publishers. 2011.
1194:
1184:
849:
601:
67:Thalassemia minor, intermediate and major
3282:The MGH Review of Critical Care Medicine
3064:
2756:
2750:
2085:(7th ed.). Philadelphia: Saunders.
2076:
2074:
1551:Molecular Pathology in Clinical Practice
1360:
1358:
1356:
1354:
1352:
1350:
1348:
1346:
1344:
1342:
1340:
1338:
1336:
1334:
605:
484:and right-upper quadrant pain caused by
467:
391:
160:
3435:Cao, Antonio; Galanello, Renzo (2010).
2949:. In Holzheimer RG, Mannick JA (eds.).
1547:
1332:
1330:
1328:
1326:
1324:
1322:
1320:
1318:
1316:
1314:
4204:
2609:
2549:
1859:
1717:
1244:
1053:
1051:
1049:
412:. DNA contains both the instructions (
3744:
3670:
3445:. University of Washington, Seattle.
3285:. Lippincott Williams & Wilkins.
3071:. Lippincott Williams & Wilkins.
2823:from the original on 22 November 2023
2738:from the original on 25 November 2023
2692:
2357:. Lippincott Williams & Wilkins.
2319:. Lippincott Williams & Wilkins.
2071:
2011:from the original on 20 November 2016
1695:. Lippincott Williams & Wilkins.
1619:. Lippincott Williams & Wilkins.
1248:Oxford Handbook of Clinical Pathology
1119:
1117:
156:
3848:triosephosphate isomerase deficiency
2896:from the original on 9 December 2023
2860:from the original on 8 December 2023
2797:from the original on 4 December 2023
2705:from the original on 4 December 2023
1311:
736:technology to be approved by the US
384:and none in the preceding 2 months.
4003:paroxysmal nocturnal hemoglobinuria
3971:Donath–Landsteiner hemolytic anemia
3951:
3014:Cappellini, Maria Domenica (2007).
2734:(Press release). 16 November 2023.
1548:Leonard, Debra G. B. (2007-11-25).
1486:Handbook of Iron Overload Disorders
1046:
13:
3427:
3186:
2982:
2580:Kansteiner, Fraiser (2022-08-17).
2531:from the original on 28 April 2024
2179:European Journal of Human Genetics
1114:
1089:
904:) is the Greek word for blood. In
749:hematopoietic stem cell transplant
14:
4233:
4012:Microangiopathic hemolytic anemia
3983:Mixed autoimmune hemolytic anemia
3511:
3411:from the original on 4 April 2017
3141:Brissot P, Cappellini MD (2014).
2995:from the original on 4 April 2017
2383:. ScholarlyEditions. 2012-01-09.
1979:. ScholarlyEditions. 2013-07-22.
1102:from the original on 4 April 2017
864:non-alcoholic fatty liver disease
776:
648:preimplantation genetic diagnosis
4043:Hemolytic disease of the newborn
3640:
2870:
448:to make that single correction.
387:
3382:from the original on 2013-11-04
3363:
3352:from the original on 2023-01-14
3325:
3299:
3272:
3243:
3201:
3180:
3134:
3123:from the original on 2023-01-14
3106:Blood and Bone Marrow Pathology
3096:
3085:from the original on 2023-01-14
3058:
3007:
2976:
2957:
2938:
2927:from the original on 2024-01-17
2917:"FDA Roundup: January 16, 2024"
2908:
2882:
2717:
2675:from the original on 2023-03-27
2657:
2646:from the original on 2023-03-27
2603:
2592:from the original on 2023-01-25
2573:
2562:from the original on 2023-08-04
2543:
2519:Karen Weintraub (14 Jun 2022).
2512:
2501:from the original on 2016-03-04
2487:
2438:
2412:
2397:
2371:
2344:
2333:from the original on 2023-01-14
2306:
2295:from the original on 2019-12-15
2215:
2166:
2155:from the original on 2023-01-14
2128:
2117:from the original on 2015-05-25
2099:
2052:
2041:from the original on 2017-07-28
2023:
1993:
1967:
1956:from the original on 2023-01-14
1939:Avery's Diseases of the Newborn
1929:
1918:from the original on 2023-01-14
1891:
1880:from the original on 2023-01-14
1853:
1842:from the original on 2015-05-11
1824:
1682:
1671:from the original on 2023-01-14
1644:
1633:from the original on 2023-01-14
1606:
1579:
1568:from the original on 2023-01-14
1541:
1514:
1503:from the original on 2023-01-14
1476:
1465:from the original on 2023-01-14
1438:
1427:from the original on 2023-01-14
1367:New England Journal of Medicine
1265:from the original on 2023-01-14
1144:from the original on 2023-01-14
1069:from the original on 2015-05-13
873:
802:human activin receptor type IIB
574:
451:
3976:Paroxysmal cold hemoglobinuria
3068:The 5 Minute Pediatric Consult
2354:Wintrobe's Clinical Hematology
2316:Wintrobe's Clinical Hematology
2135:Schrijver, Iris (2011-09-09).
1860:Okpala, Iheanyi (2008-04-15).
1784:"The pathobiology of splicing"
1692:Professional Guide to Diseases
1657:. Cambridge University Press.
1489:. Cambridge University Press.
1401:
1276:
1238:
1211:
767:
442:single-nucleotide polymorphism
1:
3065:Schwartz, M. William (2012).
2985:"Beta Thalassemia Medication"
2550:Myshko, Denise (2022-04-13).
1297:10.1016/S0140-6736(22)00536-0
1039:
670:Weill Cornell Medical College
587:
4217:Hereditary hemolytic anemias
3927:Southeast Asian ovalocytosis
3915:Minkowski–Chauffard syndrome
3370:Weatherall, David J (2010).
3109:. Elsevier Health Sciences.
2852:Food and Drug Administration
2757:Sheridan C (November 2023).
2463:10.1182/blood-2010-09-306829
2273:"Alpha and Beta Thalassemia"
1942:. Elsevier Health Sciences.
1616:NORD Guide to Rare Disorders
1527:. Elsevier Health Sciences.
1245:Carton, James (2012-02-16).
1224:. Elsevier Health Sciences.
1130:. Elsevier Health Sciences.
1003:
738:Food and Drug Administration
596:
463:
250:
7:
3311:. AuthorHouse. 2013-02-06.
3194:Online Etymology Dictionary
2693:Stein R (31 October 2023).
2610:Zipkin, Mark (2019-12-06).
1012:
916:coastal regions. The major
813:Beta thalassemia intermedia
758:
531:total iron-binding capacity
93:Depends on type (see types)
10:
4238:
4036:Drug-induced nonautoimmune
4017:Thrombotic microangiopathy
3843:pyruvate kinase deficiency
3217:
3209:
2972:(2nd ed.). NBK173967.
2904:– via Business Wire.
2831:– via Business Wire.
2775:10.1038/d41587-023-00016-6
2624:10.1038/d41587-019-00035-2
784:magnetic resonance imaging
707:gene have been developed.
519:hemoglobin electrophoresis
210:. Severe symptoms include
139:ineffective erythropoiesis
4164:
4104:
4055:
4022:Hemolytic–uremic syndrome
3942:
3934:Hereditary stomatocytosis
3922:Hereditary elliptocytosis
3815:
3800:
3753:
3737:
3708:
3600:
3519:
3033:10.2147/tcrm.2007.3.2.291
2945:Uranüs S, Sill H (2001).
2277:American Family Physician
2240:10.1007/s12687-011-0069-6
1866:. John Wiley & Sons.
501:, maxillary hyperplasia,
444:), on-going efforts seek
89:
79:
75:Mutations in the HBB gene
71:
63:
51:
46:
37:
29:
24:
3910:Hereditary spherocytosis
3338:. Universal-Publishers.
1788:The Journal of Pathology
1751:10.1182/blood.2023020683
860:chronic hepatitis C
856:chronic hepatitis B
753:exagamglogene autotemcel
734:CRISPR/Cas9 gene editing
730:Exagamglogene autotemcel
709:Exagamglogene autotemcel
690:betibeglogene autotemcel
312:value (<80 fL).
245:
218:, and in extreme cases,
4115:Mean corpuscular volume
4079:Diamond–Blackfan anemia
4031:Drug-induced autoimmune
3966:Cold agglutinin disease
3772:Plummer–Vinson syndrome
3233:A Greek–English Lexicon
1832:"the definition of dna"
1063:Genetics Home Reference
980:Evolutionary adaptation
868:alcoholic liver disease
652:human leukocyte antigen
620:Bone marrow transplants
553:and slightly increased
310:mean corpuscular volume
33:Microcytemia, beta type
3767:Iron-deficiency anemia
1186:10.1186/1750-1172-5-11
1127:Maternal-Child Nursing
996:affecting hemoglobin,
990:heterozygous advantage
850:Beta thalassemia minor
836:compound heterozygotes
717:Vertex Pharmaceuticals
611:
602:Beta thalassemia major
539:peripheral blood smear
513:. These tests include
511:differential diagnosis
476:Abdominal pain due to
473:
397:
324:Thalassemia intermedia
176:compound heterozygotes
166:
4086:Pure red cell aplasia
3853:hexokinase deficiency
3465:Nature Communications
3308:Haematology Made Easy
3224:Liddell, Henry George
1379:10.1056/NEJMra2021838
950:Mediterranean peoples
918:Mediterranean islands
673:β-globin production.
609:
471:
395:
164:
4091:Sideroblastic anemia
3899:Hemoglobin C disease
3785:Megaloblastic anemia
2763:Nature Biotechnology
2616:Nature Biotechnology
2191:10.1038/ejhg.2010.90
838:have been reported.
830:; however, dominant
646:can be conceived by
515:complete blood count
187:(hypersplenism) and
113:. They are forms of
3890:Sickle cell disease
3485:10.1038/ncomms13304
3477:2016NatCo...713304B
3376:Williams Hematology
3261:on October 30, 2011
2856:. 8 December 2023.
1173:Orphanet J Rare Dis
1024:Anisopoikilocytosis
998:sickle-cell disease
842:is recommended and
828:autosomal recessive
721:CRISPR Therapeutics
545:, or target cells;
503:dental malocclusion
4177:Sulfhemoglobinemia
3601:External resources
3437:"Beta-Thalassemia"
2064:2015-09-28 at the
1904:. JP Medical Ltd.
1291:(10343): 2310–24.
1169:"Beta-thalassemia"
1059:"Beta thalassemia"
974:alpha-thalassaemia
844:prenatal diagnosis
840:Genetic counseling
826:. Transmission is
703:by inhibiting the
701:sickle cell anemia
637:The oral chelator
616:blood transfusions
612:
551:hemoglobin A2
482:splenic infarction
474:
402:messenger-type RNA
398:
240:hepatosplenomegaly
198:Excess iron (from
193:hyperbilirubinemia
167:
157:Signs and symptoms
4199:
4198:
4195:
4194:
4182:Reticulocytopenia
4172:Methemoglobinemia
4160:
4159:
4051:
4050:
3991:
3990:
3790:Pernicious anemia
3733:
3732:
3725:Polycythemia vera
3635:
3634:
3345:978-1-61233-192-8
3318:978-1-4772-4651-1
3292:978-1-4511-7368-0
3187:Harper, Douglas.
3158:978-9963-717-06-4
3116:978-0-7020-4535-6
3078:978-1-4511-1656-4
2390:978-1-4649-5208-1
2364:978-1-4698-4622-4
2326:978-1-4698-4622-4
2228:J Community Genet
2148:978-3-642-19677-5
2111:www.nhlbi.nih.gov
2092:978-1-4160-3430-8
2035:www.nhlbi.nih.gov
1986:978-1-4816-6347-2
1949:978-0-7216-9347-7
1911:978-93-5025-488-2
1873:978-1-4051-4020-1
1800:10.1002/path.2649
1702:978-0-7817-7899-2
1664:978-0-521-59380-9
1626:978-0-7817-3063-1
1599:978-1-4615-6713-4
1561:978-0-387-33227-7
1534:978-0-323-08854-1
1496:978-1-139-48939-3
1458:978-1-60327-484-5
1420:978-0-7637-9908-3
1258:978-0-19-162993-8
1231:978-0-323-32285-0
1137:978-0-323-29377-8
1029:Delta-thalassemia
1019:Alpha-thalassemia
896:word for sea and
824:chelation therapy
555:hemoglobin F
541:, which may show
523:serum transferrin
381:
380:
368:blood transfusion
344:Thalassemia major
306:microcytic anemia
293:Thalassemia minor
106:) are a group of
100:Beta thalassemias
97:
96:
81:Diagnostic method
19:Medical condition
4229:
3949:
3948:
3863:hemoglobinopathy
3813:
3812:
3751:
3750:
3742:
3741:
3713:
3712:
3691:
3684:
3677:
3668:
3667:
3658:Beta thalassemia
3644:
3643:
3517:
3516:
3506:
3496:
3454:
3421:
3420:
3418:
3416:
3397:
3391:
3390:
3388:
3387:
3367:
3361:
3360:
3358:
3357:
3329:
3323:
3322:
3303:
3297:
3296:
3276:
3270:
3269:
3267:
3266:
3257:. Archived from
3247:
3241:
3220:
3219:
3212:
3211:
3205:
3199:
3198:
3184:
3178:
3177:
3175:
3174:
3138:
3132:
3131:
3129:
3128:
3100:
3094:
3093:
3091:
3090:
3062:
3056:
3055:
3045:
3035:
3011:
3005:
3004:
3002:
3000:
2980:
2974:
2973:
2961:
2955:
2954:
2942:
2936:
2935:
2933:
2932:
2912:
2906:
2905:
2903:
2901:
2886:
2880:
2874:
2873:
2869:
2867:
2865:
2842:
2833:
2832:
2830:
2828:
2813:
2807:
2806:
2804:
2802:
2754:
2748:
2747:
2745:
2743:
2721:
2715:
2714:
2712:
2710:
2690:
2684:
2683:
2681:
2680:
2661:
2655:
2654:
2652:
2651:
2607:
2601:
2600:
2598:
2597:
2577:
2571:
2570:
2568:
2567:
2547:
2541:
2540:
2538:
2536:
2516:
2510:
2509:
2507:
2506:
2491:
2485:
2484:
2474:
2442:
2436:
2435:
2416:
2410:
2401:
2395:
2394:
2375:
2369:
2368:
2348:
2342:
2341:
2339:
2338:
2310:
2304:
2303:
2301:
2300:
2268:
2262:
2261:
2251:
2219:
2213:
2212:
2202:
2170:
2164:
2163:
2161:
2160:
2132:
2126:
2125:
2123:
2122:
2103:
2097:
2096:
2078:
2069:
2056:
2050:
2049:
2047:
2046:
2027:
2021:
2020:
2018:
2016:
1997:
1991:
1990:
1971:
1965:
1964:
1962:
1961:
1933:
1927:
1926:
1924:
1923:
1895:
1889:
1888:
1886:
1885:
1857:
1851:
1850:
1848:
1847:
1828:
1822:
1821:
1811:
1779:
1773:
1772:
1762:
1730:
1715:
1714:
1686:
1680:
1679:
1677:
1676:
1648:
1642:
1641:
1639:
1638:
1610:
1604:
1603:
1583:
1577:
1576:
1574:
1573:
1545:
1539:
1538:
1518:
1512:
1511:
1509:
1508:
1480:
1474:
1473:
1471:
1470:
1442:
1436:
1435:
1433:
1432:
1405:
1399:
1398:
1362:
1309:
1308:
1280:
1274:
1273:
1271:
1270:
1242:
1236:
1235:
1215:
1209:
1208:
1198:
1188:
1164:
1153:
1152:
1150:
1149:
1121:
1112:
1111:
1109:
1107:
1087:
1078:
1077:
1075:
1074:
1055:
1034:Hemoglobinopathy
994:genetic disorder
970:Turkish Cypriots
846:may be offered.
697:fetal hemoglobin
537:and urobilogen;
416:) for stringing
346:
345:
326:
325:
295:
294:
274:
273:
208:endocrine glands
147:iron homeostasis
42:
25:Beta-thalassemia
22:
21:
4237:
4236:
4232:
4231:
4230:
4228:
4227:
4226:
4202:
4201:
4200:
4191:
4156:
4100:
4059:
4047:
3987:
3938:
3804:
3796:
3729:
3704:
3702:red blood cells
3695:
3665:
3664:
3663:
3645:
3641:
3636:
3631:
3630:
3596:
3595:
3528:
3514:
3509:
3430:
3428:Further reading
3425:
3424:
3414:
3412:
3399:
3398:
3394:
3385:
3383:
3368:
3364:
3355:
3353:
3346:
3330:
3326:
3319:
3305:
3304:
3300:
3293:
3277:
3273:
3264:
3262:
3249:
3248:
3244:
3238:Perseus Project
3206:
3202:
3185:
3181:
3172:
3170:
3159:
3143:"Liver Disease"
3139:
3135:
3126:
3124:
3117:
3101:
3097:
3088:
3086:
3079:
3063:
3059:
3012:
3008:
2998:
2996:
2983:Advani, Pooja.
2981:
2977:
2962:
2958:
2943:
2939:
2930:
2928:
2913:
2909:
2899:
2897:
2888:
2887:
2883:
2871:
2863:
2861:
2844:
2843:
2836:
2826:
2824:
2815:
2814:
2810:
2800:
2798:
2755:
2751:
2741:
2739:
2723:
2722:
2718:
2708:
2706:
2691:
2687:
2678:
2676:
2663:
2662:
2658:
2649:
2647:
2608:
2604:
2595:
2593:
2578:
2574:
2565:
2563:
2548:
2544:
2534:
2532:
2517:
2513:
2504:
2502:
2493:
2492:
2488:
2443:
2439:
2418:
2417:
2413:
2402:
2398:
2391:
2377:
2376:
2372:
2365:
2349:
2345:
2336:
2334:
2327:
2311:
2307:
2298:
2296:
2269:
2265:
2220:
2216:
2185:(10): 1077–83.
2171:
2167:
2158:
2156:
2149:
2133:
2129:
2120:
2118:
2105:
2104:
2100:
2093:
2079:
2072:
2066:Wayback Machine
2057:
2053:
2044:
2042:
2029:
2028:
2024:
2014:
2012:
1999:
1998:
1994:
1987:
1973:
1972:
1968:
1959:
1957:
1950:
1934:
1930:
1921:
1919:
1912:
1896:
1892:
1883:
1881:
1874:
1858:
1854:
1845:
1843:
1830:
1829:
1825:
1780:
1776:
1745:(11): 949–960.
1731:
1718:
1703:
1687:
1683:
1674:
1672:
1665:
1649:
1645:
1636:
1634:
1627:
1611:
1607:
1600:
1584:
1580:
1571:
1569:
1562:
1546:
1542:
1535:
1519:
1515:
1506:
1504:
1497:
1481:
1477:
1468:
1466:
1459:
1443:
1439:
1430:
1428:
1421:
1407:
1406:
1402:
1363:
1312:
1281:
1277:
1268:
1266:
1259:
1243:
1239:
1232:
1216:
1212:
1165:
1156:
1147:
1145:
1138:
1122:
1115:
1105:
1103:
1090:Advani, Pooja.
1088:
1081:
1072:
1070:
1057:
1056:
1047:
1042:
1015:
1006:
982:
876:
852:
815:
779:
770:
761:
604:
599:
590:
577:
565:Chipmunk facies
466:
454:
404:(mRNA) that is
390:
360:Homozygous form
343:
342:
336:
323:
322:
316:
292:
291:
280:Older synonyms
253:
248:
212:liver cirrhosis
159:
145:, and deranged
111:blood disorders
20:
17:
12:
11:
5:
4235:
4225:
4224:
4219:
4214:
4197:
4196:
4193:
4192:
4190:
4189:
4184:
4179:
4174:
4168:
4166:
4162:
4161:
4158:
4157:
4155:
4154:
4153:
4152:
4147:
4135:
4134:
4133:
4128:
4123:
4110:
4108:
4102:
4101:
4099:
4098:
4093:
4088:
4081:
4076:
4074:Fanconi anemia
4067:
4065:
4053:
4052:
4049:
4048:
4046:
4045:
4039:
4038:
4033:
4027:
4026:
4025:
4024:
4014:
4008:
4007:
4006:
4005:
3992:
3989:
3988:
3986:
3985:
3980:
3979:
3978:
3968:
3963:
3957:
3955:
3946:
3940:
3939:
3937:
3936:
3931:
3930:
3929:
3919:
3918:
3917:
3901:
3896:
3887:
3886:
3885:
3880:
3875:
3858:
3857:
3856:
3855:
3850:
3845:
3833:
3821:
3819:
3810:
3798:
3797:
3795:
3794:
3793:
3792:
3777:
3776:
3775:
3774:
3759:
3757:
3748:
3739:
3735:
3734:
3731:
3730:
3728:
3727:
3721:
3719:
3710:
3706:
3705:
3694:
3693:
3686:
3679:
3671:
3646:
3639:
3638:
3637:
3633:
3632:
3629:
3628:
3617:
3615:article/199534
3605:
3604:
3602:
3598:
3597:
3594:
3593:
3582:
3571:
3560:
3545:
3529:
3524:
3523:
3521:
3520:Classification
3513:
3512:External links
3510:
3508:
3507:
3455:
3431:
3429:
3426:
3423:
3422:
3392:
3362:
3344:
3324:
3317:
3298:
3291:
3271:
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3200:
3179:
3157:
3133:
3115:
3095:
3077:
3057:
3006:
2975:
2956:
2937:
2907:
2881:
2834:
2808:
2749:
2716:
2685:
2671:. 2022-02-20.
2656:
2602:
2572:
2556:Managed Health
2542:
2511:
2497:. 2012-03-28.
2486:
2457:(5): 1745–50.
2437:
2420:"Deferoxamine"
2411:
2396:
2389:
2370:
2363:
2343:
2325:
2305:
2263:
2214:
2165:
2147:
2127:
2098:
2091:
2070:
2051:
2022:
2001:"Risk Factors"
1992:
1985:
1966:
1948:
1928:
1910:
1890:
1872:
1852:
1836:Dictionary.com
1823:
1774:
1716:
1701:
1681:
1663:
1643:
1625:
1605:
1598:
1578:
1560:
1540:
1533:
1513:
1495:
1475:
1457:
1437:
1419:
1400:
1373:(8): 727–743.
1310:
1275:
1257:
1251:. OUP Oxford.
1237:
1230:
1210:
1154:
1136:
1113:
1079:
1044:
1043:
1041:
1038:
1037:
1036:
1031:
1026:
1021:
1014:
1011:
1005:
1002:
981:
978:
875:
872:
851:
848:
814:
811:
809:iron levels).
778:
777:Pharmaceutical
775:
769:
766:
760:
757:
668:Scientists at
644:savior sibling
603:
600:
598:
595:
589:
586:
576:
573:
572:
571:
568:
507:cholelithiasis
465:
462:
453:
450:
446:gene therapies
420:together into
389:
386:
379:
378:
375:
357:
347:
339:
338:
333:
330:
327:
319:
318:
313:
299:
296:
288:
287:
284:
281:
278:
269:
268:
261:
252:
249:
247:
244:
228:erythropoiesis
224:red blood cell
216:liver fibrosis
158:
155:
104:β thalassemias
95:
94:
91:
87:
86:
83:
77:
76:
73:
69:
68:
65:
61:
60:
55:
49:
48:
44:
43:
35:
34:
31:
27:
26:
18:
16:Blood disorder
15:
9:
6:
4:
3:
2:
4234:
4223:
4222:Rare diseases
4220:
4218:
4215:
4213:
4210:
4209:
4207:
4188:
4185:
4183:
4180:
4178:
4175:
4173:
4170:
4169:
4167:
4163:
4151:
4148:
4146:
4143:
4142:
4141:
4140:
4136:
4132:
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4127:
4124:
4122:
4119:
4118:
4117:
4116:
4112:
4111:
4109:
4107:
4103:
4097:
4096:Myelophthisic
4094:
4092:
4089:
4087:
4083:
4082:
4080:
4077:
4075:
4071:
4068:
4066:
4063:
4058:
4054:
4044:
4041:
4040:
4037:
4034:
4032:
4029:
4028:
4023:
4020:
4019:
4018:
4015:
4013:
4010:
4009:
4004:
4001:
4000:
3999:
3998:
3994:
3993:
3984:
3981:
3977:
3974:
3973:
3972:
3969:
3967:
3964:
3962:
3959:
3958:
3956:
3954:
3950:
3947:
3945:
3941:
3935:
3932:
3928:
3925:
3924:
3923:
3920:
3916:
3913:
3912:
3911:
3908:
3906:
3902:
3900:
3897:
3895:
3891:
3888:
3884:
3881:
3879:
3876:
3874:
3871:
3870:
3869:
3866:
3864:
3860:
3859:
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3849:
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3840:
3839:
3838:
3834:
3832:
3829:
3827:
3823:
3822:
3820:
3818:
3814:
3811:
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3803:
3799:
3791:
3788:
3787:
3786:
3782:
3779:
3778:
3773:
3770:
3769:
3768:
3764:
3761:
3760:
3758:
3756:
3752:
3749:
3747:
3743:
3740:
3736:
3726:
3723:
3722:
3720:
3718:
3714:
3711:
3707:
3703:
3699:
3692:
3687:
3685:
3680:
3678:
3673:
3672:
3669:
3661:
3660:
3659:
3653:
3649:
3627:
3623:
3622:
3618:
3616:
3612:
3611:
3607:
3606:
3603:
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3588:
3587:
3583:
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3570:
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3565:
3561:
3559:
3555:
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3540:
3539:
3535:
3531:
3530:
3527:
3522:
3518:
3504:
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3490:
3486:
3482:
3478:
3474:
3470:
3466:
3462:
3456:
3452:
3448:
3444:
3443:
3438:
3433:
3432:
3410:
3406:
3402:
3396:
3381:
3377:
3373:
3366:
3351:
3347:
3341:
3337:
3336:
3328:
3320:
3314:
3310:
3309:
3302:
3294:
3288:
3284:
3283:
3275:
3260:
3256:
3252:
3246:
3239:
3235:
3234:
3229:
3228:Scott, Robert
3225:
3221:
3213:
3204:
3196:
3195:
3190:
3189:"thalassemia"
3183:
3168:
3164:
3160:
3154:
3150:
3149:
3144:
3137:
3122:
3118:
3112:
3108:
3107:
3099:
3084:
3080:
3074:
3070:
3069:
3061:
3053:
3049:
3044:
3039:
3034:
3029:
3025:
3021:
3017:
3010:
2994:
2990:
2986:
2979:
2971:
2967:
2960:
2952:
2948:
2941:
2926:
2922:
2918:
2911:
2895:
2891:
2885:
2878:
2877:public domain
2859:
2855:
2853:
2847:
2841:
2839:
2822:
2818:
2812:
2796:
2792:
2788:
2784:
2780:
2776:
2772:
2768:
2764:
2760:
2753:
2737:
2733:
2731:
2726:
2720:
2704:
2700:
2696:
2689:
2674:
2670:
2666:
2660:
2645:
2641:
2637:
2633:
2629:
2625:
2621:
2617:
2613:
2606:
2591:
2587:
2586:Fierce Pharma
2583:
2576:
2561:
2557:
2553:
2546:
2530:
2526:
2522:
2515:
2500:
2496:
2490:
2482:
2478:
2473:
2468:
2464:
2460:
2456:
2452:
2448:
2441:
2433:
2429:
2425:
2421:
2415:
2409:
2405:
2400:
2392:
2386:
2382:
2381:
2374:
2366:
2360:
2356:
2355:
2347:
2332:
2328:
2322:
2318:
2317:
2309:
2294:
2290:
2286:
2283:(4): 339–44.
2282:
2278:
2274:
2267:
2259:
2255:
2250:
2245:
2241:
2237:
2233:
2229:
2225:
2218:
2210:
2206:
2201:
2196:
2192:
2188:
2184:
2180:
2176:
2169:
2154:
2150:
2144:
2140:
2139:
2131:
2116:
2112:
2108:
2102:
2094:
2088:
2084:
2077:
2075:
2067:
2063:
2060:
2055:
2040:
2036:
2032:
2026:
2010:
2006:
2002:
1996:
1988:
1982:
1978:
1977:
1970:
1955:
1951:
1945:
1941:
1940:
1932:
1917:
1913:
1907:
1903:
1902:
1894:
1879:
1875:
1869:
1865:
1864:
1856:
1841:
1837:
1833:
1827:
1819:
1815:
1810:
1805:
1801:
1797:
1794:(2): 152–63.
1793:
1789:
1785:
1778:
1770:
1766:
1761:
1756:
1752:
1748:
1744:
1740:
1736:
1729:
1727:
1725:
1723:
1721:
1712:
1708:
1704:
1698:
1694:
1693:
1685:
1670:
1666:
1660:
1656:
1655:
1647:
1632:
1628:
1622:
1618:
1617:
1609:
1601:
1595:
1591:
1590:
1582:
1567:
1563:
1557:
1553:
1552:
1544:
1536:
1530:
1526:
1525:
1517:
1502:
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1487:
1479:
1464:
1460:
1454:
1450:
1449:
1441:
1426:
1422:
1416:
1412:
1411:
1404:
1396:
1392:
1388:
1384:
1380:
1376:
1372:
1368:
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1359:
1357:
1355:
1353:
1351:
1349:
1347:
1345:
1343:
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1337:
1335:
1333:
1331:
1329:
1327:
1325:
1323:
1321:
1319:
1317:
1315:
1306:
1302:
1298:
1294:
1290:
1286:
1279:
1264:
1260:
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1250:
1249:
1241:
1233:
1227:
1223:
1222:
1214:
1206:
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1192:
1187:
1182:
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1174:
1170:
1163:
1161:
1159:
1143:
1139:
1133:
1129:
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1118:
1101:
1097:
1093:
1086:
1084:
1068:
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1052:
1050:
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1035:
1032:
1030:
1027:
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1020:
1017:
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1010:
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999:
995:
991:
987:
977:
975:
971:
967:
963:
959:
955:
951:
947:
943:
939:
935:
931:
927:
923:
919:
915:
911:
907:
903:
899:
895:
891:
887:
886:
881:
880:Mediterranean
871:
869:
865:
861:
857:
847:
845:
841:
837:
833:
829:
825:
821:
820:iron overload
810:
807:
803:
799:
795:
793:
789:
785:
774:
765:
756:
754:
750:
746:
741:
739:
735:
731:
727:
724:
722:
718:
714:
710:
706:
702:
698:
693:
691:
687:
683:
679:
674:
671:
666:
664:
660:
655:
653:
649:
645:
640:
635:
633:
629:
625:
624:iron overload
621:
617:
608:
594:
585:
583:
569:
566:
563:
562:
561:
558:
556:
552:
548:
544:
540:
536:
532:
528:
524:
520:
516:
512:
508:
504:
500:
496:
492:
487:
483:
479:
478:hypersplenism
470:
461:
458:
449:
447:
443:
438:
434:
429:
427:
424:, as well as
423:
419:
415:
411:
407:
403:
394:
388:mRNA assembly
385:
376:
373:
369:
365:
361:
358:
355:
351:
350:Mediterranean
348:
341:
340:
334:
331:
328:
321:
320:
314:
311:
307:
303:
300:
297:
290:
289:
285:
282:
279:
276:
275:
272:
266:
262:
258:
257:
256:
243:
241:
235:
233:
229:
225:
221:
217:
213:
209:
205:
201:
196:
194:
190:
186:
181:
177:
173:
172:heart failure
163:
154:
152:
151:iron overload
148:
144:
140:
136:
131:
128:
124:
120:
116:
112:
109:
105:
101:
92:
88:
84:
82:
78:
74:
70:
66:
62:
59:
56:
54:
50:
45:
41:
36:
32:
28:
23:
4145:normochromic
4137:
4113:
3995:
3903:
3877:
3861:
3835:
3824:
3717:Polycythemia
3656:
3655:
3654:profile for
3651:
3619:
3608:
3584:
3573:
3562:
3547:
3532:
3468:
3464:
3441:
3413:. Retrieved
3405:ScienceDaily
3404:
3395:
3384:. Retrieved
3375:
3365:
3354:. Retrieved
3334:
3327:
3307:
3301:
3281:
3274:
3263:. Retrieved
3259:the original
3254:
3245:
3231:
3203:
3192:
3182:
3171:. Retrieved
3147:
3136:
3125:. Retrieved
3105:
3098:
3087:. Retrieved
3067:
3060:
3026:(2): 291–9.
3023:
3019:
3009:
2997:. Retrieved
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559:
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364:splenomegaly
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220:liver cancer
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180:heterozygous
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141:, increased
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4150:hypochromic
4106:Blood tests
3868:Thalassemia
3826:enzymopathy
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3442:GeneReviews
3255:www.who.int
3169:. NBK269366
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768:Therapeutic
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632:deferiprone
418:amino acids
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4206:Categories
4131:macrocytic
4126:microcytic
4121:normocytic
4084:Acquired:
4070:Hereditary
3837:glycolysis
3817:Hereditary
3586:DiseasesDB
3386:2012-10-02
3356:2020-10-25
3265:2015-05-26
3173:2023-12-09
3127:2020-10-25
3089:2020-10-25
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2709:4 December
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2121:2015-05-26
2045:2015-05-26
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1922:2020-10-25
1884:2020-10-25
1846:2015-05-26
1675:2020-10-25
1637:2020-10-25
1572:2020-10-25
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1269:2020-10-25
1148:2020-10-25
1073:2015-05-26
1040:References
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108:inherited
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4060:(mostly
4057:Aplastic
3997:membrane
3944:Acquired
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3805:(mostly
3698:Diseases
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