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Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:140700]. This is a form of
non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit,
basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy,
diffuse or punctate basophilia may be evident. Most of these cases are probably instances of
hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with
the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency.
Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:604131]. A form of thalassemia.
Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian
populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the
adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of
detectable beta globin causes beta+-thalassemia. In the severe forms of beta-thalassemia, the excess
alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their
deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective
erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided
into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate
severity), and thalassemia minor that is asymptomatic.
Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:603903]; also known as sickle
cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in
chronic anemia and periodic episodes of pain, serious infections and damage to vital organs.
Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle
cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They
are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular
occlusion thus cutting off the blood supply to nearby tissues.
Defects in HBB are the cause of beta-thalassemia dominant inclusion body type (B-THALIB) [MIM:603902].
An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice,
cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia
of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of
large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood
after splenectomy.
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