Disease #00001

Official abbreviation beta-thal
Name beta thalassemia
OMIM ID 141900
Human Phenotype Ontology Project (HPO) HPO
Individuals reported having this disease 0
Phenotype entries for this disease 0
Associated with 1 gene HBB
Associated tissues bone marrow
Disease features ß-thalassemias are characterized by quantitative reduction in the production of ß-globin chains of HbA, which leads to hypochromic, microcytic anemia with low mean corpuscular Hb concentration in affected erythrocytes. Point mutations within the HBB gene or its flanking sequences are the main cause of ß-thalassemias; however, small deletions involving the gene may also occur.
Most ß-thalassemias are inherited in an autosomal recessive pattern but there is a subgroup in which mutant alleles act as dominant negatives. Absence or decreased synthesis of ß-globin chains lead to accumulation of α-globin chains, resulting in the pathophysiology of this disorder. The severity of the disease is generally determined by the degree of imbalance between α and non- α-globin chain synthesis and the size of the free α-chain pool.
ß-thalassemias are classified into three main groups according to their clinical expression: major, intermedia and minor, depending on the combination of the inherited ß-alleles (ß0, ß+, ß++). ß0 variants lead to complete absence of ß-globin chains, while in the presence of ß+ variants the production of ß-globin chains is reduced. On the other hand, ß++ alleles have only subtle effects on their production.
ß-thalassemia major courses with severe phenotype and is associated mostly with ß0 variants in the homozygous or compound heterozygous state. ß-thalassemia intermedia presents with a less severe phenotype, usually associated with ß+ and ß++ variants. However, patients who harbor the same mutation may present different clinical expression, once genetic modifiers may be involved, for example by the interaction with α-thalassemia and increased production of γ-chains, which can ameliorate the severity of ß-thalassemia.

Thein SL, Wood WG. The molecular basis of ß thalassemia, δß thalassemia, and hereditary persistence of fetal hemoglobin. In: Steinberg MH, Forget BG, Higgs DR, Weatherall DJ, editors. Disorders of Hemoglobin – Genetics, pathophysiology, and clinical management. 2nd Edition. Cambridge University Press; 2009:323-356.
Origa R. Beta-thalassemia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
Mettananda S, Higgs DR. Molecular basis and genetic modifiers of thalassemia. Hematol Oncol Clin North Am. 2018;32(2):177-191.
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