thalassemia

Hemoglobin consists of two alpha subunits and two beta subunits (each of the four subunits is marked with a different color, although they always occur as two identical pairs). A defect in the production of one of these subunits results in thalassemia.

Thalassemia is a collective term for several inherited blood disorders that arise due to impaired production of one of the components of hemoglobin, the blood pigment. It manifests as anemia and related complications, with varying degrees of severity. In typical cases, the disease results from a defect in the production of the protein subunit α (α-thalassemia) or β (β-thalassemia); γ and δ subunit defects rarely cause thalassemia.

Thalassemia belongs to the group of hemoglobinopathies—conditions in which hemoglobin is structurally or functionally abnormal. There is a partial or complete deficiency of hemoglobin subunits, leading to impaired oxygen transport to tissues.

Diagnosis:
Thalassemias arise from mutations in the genes responsible for the corresponding hemoglobin subunits. If one allele of a gene is mutated, it is referred to as minor (heterozygous) thalassemia; when both alleles are mutated, it is called major thalassemia (homozygous).

Homozygous α-thalassemia is usually incompatible with life (the fetus often dies in utero due to severe oxygen deficiency). Homozygous β-thalassemia also has a very severe course and in females can lead to infertility. Heterozygous thalassemia generally has a much milder clinical course.

Treatment:
Treatment depends on the severity and associated complications. It may include blood transfusions, splenectomy (surgical removal of the spleen), treatment of liver disease and chronic hepatitis, and management of other complications. In some cases, hematopoietic stem cell transplantation is used.

• Symptoms of alpha thalassemia:
• anemia – depending on severity, it may be asymptomatic or cause shortness of breath, pale skin and conjunctiva, palpitations, fainting and collapse, tinnitus, fatigue, weakness
• weight loss, failure to thrive
• hepatomegaly (enlarged liver), splenomegaly (enlarged spleen)
• leg ulcers
• bone marrow exhaustion/ineffective hematopoiesis leading to infections, anemia, bleeding
• skeletal developmental changes and metabolic disturbances
• osteopenia and increased bone fragility
• compression fractures of vertebrae
• ribs with a more angular, “box-like” shape
• Symptoms of beta thalassemia:
• anemia of varying severity, ineffective erythropoiesis (red blood cell production)
• jaundice due to increased breakdown of red blood cells
• heart failure and arrhythmias
• chronic hepatitis, hepatomegaly, and changes in the gallbladder and spleen