Hemoglobin C without Hemoglobin A

An individual with hemoglobin C as the principal hemoglobin but no hemoglobin A may have either homozygous hemoglobin C (C/C), or hemoglobin C/beta⁰-thalassemia. Either diagnosis is associated with few clinical manifestations. The best method to distinguish these is to test both parents.

Hemoglobin C is the second most common hemoglobin variant found in the United States next to sickle hemoglobin. Hemoglobin C is found primarily in African-Americans. Approximately 2-3% of African Americans are A/C heterozygotes.

The beta chain of hemoglobin C contains a lysine substituted for the glutamic acid A in the sixth position. This substitution gives hemoglobin C a relatively high positive charge and therefore slow mobility on electrophoresis. Hemoglobin C migrates with hemoglobin A2 and hemoglobin E on cellulose acetate electrophoresis (pH 8.4). The mobility of these hemoglobins differs on agar gel electrophoresis (pH 6.2) and they can be distinguished by this method. Deoxyhemoglobin C forms intracellular crystals when the concentration is > 48%.

Homozygous hemoglobin C: (C/C)
Patients who are homozygous for hemoglobin C are usually asymptomatic and may have a mild to moderate hemolytic anemia. The following manifestations have been reported:

• enlarged spleen
• packed cell volume ~25-30%
• moderate reticulocytosis
• peripheral blood film showing target cells, microspherocytes and intracellular crystals

Hemoglobin C/ beta-thalassemia: (C/beta-thal)
Patients who are heterozygous for hemoglobin C and beta-thalassemia are generally asymptomatic and have moderate hemolytic anemia. Those with hemoglobin C/beta⁺-thalassemia (some hemoglobin A present) tend to have mild anemia and the spleen is usually not palpable. In individuals with hemoglobin C/beta⁰-thalassemia (no hemoglobin A present), the anemia is more marked and the spleen is usually enlarged.

References

1. Bunn and Forget: Hemoglobin: Molecular, Genetic and Clinical Aspects. Philadelphia, W.B. Saunders Company 1986 Weatherall and Clegg: The Thalassaemia Syndromes. Oxford, Blackwell Scientific Publications 1981
2. Smith and Krevans:Clinical Manifestations of Hemoglobin C Disorders. Bulletin Johns Hopkins Hospital 104, 17-43. 1959

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