Hemoglobinopathy

Hemoglobinopathy is a group of inherited disorders involving abnormal structure of the hemoglobin molecule. Hemoglobin is the protein present in red blood cells which carries oxygen and which gives blood its color. Hemoglobin disorders include hemoglobin C disease, hemoglobin S-C disease, sickle cell anemia, and various types of thalassemia

A group of autosomal recessive disorders characterized by synthesis of abnormal hemoglobin molecules (e.g. S, C, D, & E) or decreased synthesis of alpha or beta globin chains (thalassemia). For a hemoglobinopathy disease condition to exist, an abnormal hemoglobin or thalassemia typically must be inherited from both parents resulting in a homozygous or double heterozygous condition.

Defects in these genes can produce abnormal hemoglobin, which are conditions called hemoglobinopathy. Abnormal hemoglobins appear in one of three basic circumstances:

1. Structural defects in the hemoglobin molecule. Alterations in the gene for one of the two hemoglobin subunit chains, alpha (a) or beta (b). Often, mutations change a single amino acid building block in the subunit. Most commonly the change is innocuous, perturbing neither the structure nor function of the hemoglobin molecule. Occasionally, alteration of a single amino acid dramatically disturbs the behavior of the hemoglobin molecule and produces a disease state. Sickle hemoglobin exemplifies this phenomenon.

2. Diminished production of one of the two subunits of the hemoglobin molecule. Mutations that produce this condition are called thalassemias. Equal numbers of hemoglobin alpha and beta chains are necessary for normal function. Hemoglobin chain imbalance damages and destroys red cells thereby producing anemia. Although there is a dearth of the affected hemoglobin subunit, with most thalassemias the few subunits synthesized are structurally normal.

3. Abnormal associations of otherwise normal subunits. A single subunit of the alpha chain (from the a-globin locus) and a single subunit from the b-globin locus combine to produce a normal hemoglobin dimer. With severe a-thalassemia, the b-globin subunits begin to associate into groups of four (tetramers) due to the paucity of potential a-chain partners. These tetramers of b-globin subunits are functionally inactive and do not transport oxygen. No comparable tetramers of alpha globin subunits form with severe beta-thalassemia. Alpha subunits are rapidly degraded in the absence of a partner from the beta-globin gene cluster.

Hemoglobinopathy is estimated that 7% of worlds population are carriers, with 70% pathological being in Africa. Hemoglobinopathies are most common in ethnic populations from Africa, the Mediterranean basin and Southeast Asia.