Hemoglobinopathies are genetic disorders affecting the structure or production of the hemoglobin molecule.
Hemoglobin molecules consist of polypeptide chains whose chemical structure is genetically controlled. Different hemoglobins, as distinguished by electrophoretic mobility, are alphabetically designated in order of discovery (eg, A, B, C), although the first abnormal hemoglobin to be identified, sickle cell hemoglobin, was designated hemoglobin S.
Structurally different hemoglobins with the same electrophoretic mobility are named for the city or location in which they were discovered (eg, Hb S Memphis, Hb C Harlem). Standard description of a patient’s hemoglobin composition places the hemoglobin of greatest concentration first (eg, AS in sickle cell trait).
The normal adult hemoglobin molecule (Hb A) consists of 2 pairs of chains designated alpha and beta. Normal adult blood also contains ≤ 2.5% hemoglobin A2 (composed of alpha and delta chains) and < 1.4 % hemoglobin F (fetal hemoglobin, composed of alpha and gamma chains—see also Hemoglobinopathies in Pregnancy Hemoglobinopathies in Pregnancy Normally during pregnancy, erythroid hyperplasia of the marrow occurs, and red blood cell (RBC) mass increases. However, a disproportionate increase in plasma volume results in hemodilution... read more ). Hemoglobin F predominates during gestation and gradually decreases after birth, particularly in the first months of life; its concentration increases in certain disorders of hemoglobin synthesis, some bone marrow failure disorders Aplastic Anemia Aplastic anemia is a disorder of the hematopoietic stem cell that results in a loss of blood cell precursors, hypoplasia or aplasia of bone marrow, and cytopenias in two or more cell lines ... read more , and myeloproliferative neoplasms Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow hematopoietic stem cells, which can manifest as an increased number of functionally normal platelets, red blood cells (RBCs)... read more .
Some hemoglobinopathies result in anemias that are severe in patients who are homozygous but mild in those who are heterozygous. Some patients are compound heterozygotes for 2 different hemoglobinopathies and have anemia of varying severity.
In the US, common anemias include those caused by genetic mutations resulting in sickle cell disease (Hb S disease) Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more or Hb C disease Hemoglobin C Disease Hemoglobin C disease is a hemoglobinopathy that causes symptoms of a hemolytic anemia. (See also Overview of Hemolytic Anemia.) The prevalence of detectable hemoglobin (Hb) C in people in the... read more and the thalassemias Thalassemias Thalassemias are a group of inherited microcytic, hemolytic anemias characterized by defective hemoglobin synthesis. Alpha-thalassemia is particularly common among people with African, Mediterranean... read more . Immigration to the US of people with Southeast Asian ancestry has made Hb E disease Hemoglobin E Disease Homozygous hemoglobin E (Hb E) disease is a hemoglobinopathy that causes a mild hemolytic anemia, usually without splenomegaly. (See also Overview of Hemolytic Anemia.) Hemoglobin (Hb) E is... read more common.