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Hemoglobinopathy is a genetic defect that causes abnormal structure of one of the globin chains of the hemoglobin molecule. Thalassemia is a genetic defect resulting in the production of an abnormally low quantity of a given hemoglobin chain or chains. (Table H-2)

Table H-2 Hemoglobin Disorders: An Overview

At a Glance

Genetically inherited hemolytic anemia, usually mild and often inapparent until adulthood. Mainly encountered in populations of African descent but also in populations of Sicilian and Hispanic descent.

Synonyms

CC Disease; Hemoglobinopathy C.

Nature

Hemolytic anemia with moderate reduction in red cell lifespan. In the oxyhemoglobin state, hemoglobin C is less soluble than normal hemoglobin, thus forming intraerythrocytic crystals (tactoids); deoxygenation further reduces solubility and increases blood viscosity. Patients with hemoglobin C disease have a survival advantage in areas of endemic Plasmodium falciparum malaria.

Incidence

Prevalence in the general population is 0.017% in African Americans but approximately 0.03% in Northern Africa. No sex prevalence.

Genetic Inheritance

Autosomal codominant (biparental inheritance). The beta gene cluster is on chromosome 11.

Pathophysiology

The double helix of hemoglobin C is composed of two normal alpha-chains and two variant beta-chains, in which glutamic acid is replaced by lysine at position 6. Hemoglobin C is unstable and tends to precipitate in erythrocytes where it crystallizes. This changes the physical properties of the erythrocytic membrane (decreased deformability and increased viscosity of blood). These crystal-containing red blood cells are removed by the spleen, which becomes enlarged with time (splenomegaly).

Diagnosis

Examination of the erythrocytes (blood smear) reveals several morphologic disorders (caused by crystallization of hemoglobin): target cells mainly, but also appearance of an off-center target, occasional pyknotic spherocytes, and polychromasia. Diagnosis is established by hemoglobin electrophoresis (100% hemoglobin C in homozygotes, up to 35% in heterozygotes). Reticulocyte count and lactic acid dehydrogenase levels determine the extent of hemolysis.

Clinical Aspects

Except for mild-to-moderate hemolytic anemia, most patients remain asymptomatic until adulthood. Symptoms usually consist of joint and musculoskeletal pain, visual disorders (retinopathy as a result of iron deposition in the Bruch membrane causing angioid streaks), cholelithiasis, ...

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