Hemoglobin C Disease
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《新英格兰医药杂志》
To the Editor: Although the appearance of the blood smear presented by Fairhurst and Casella (June 24 issue)1 is consistent with the presence of hemoglobin C disease, the extremely low mean corpuscular volume and the clinical scenario are more consistent with the presence of hemoglobin C -thalassemia. Hemoglobin C -thalassemia is common in African populations, and the clinical disorder is usually mild; features include low-grade anemia, a low mean corpuscular volume, and minimal elevation of the reticulocyte count, without splenomegaly. The blood smear is indistinguishable from that in hemoglobin C disease and shows microspherocytes and target cells.2 The electrophoretic pattern is dependent on whether the thalassemia is the + or 0 type. Hemoglobin electrophoresis will not differentiate hemoglobin C from hemoglobin C -thalassemia because hemoglobins C and A2 migrate together. Cation-exchange high-performance liquid chromatography is necessary to detect elevated hemoglobin A2 levels.2 In addition, in the current case, the analysis of the mother's hemoglobin may help in the diagnosis. We suspect that she would test positive for thalassemia.
Joel G. Schwab, M.D.
Herbert T. Abelson, M.D.
University of Chicago
Chicago, IL 60637
jschwab@peds.bsd.uchicago.edu
References
Fairhurst RM, Casella JF. Homozygous hemoglobin C disease. N Engl J Med 2004;350:e24-e24.
Weatherall DJ, Clegg JB. The thalassaemia syndromes. 4th ed. Oxford, England: Blackwell Science, 2001:415-9.
The authors reply: Drs. Schwab and Abelson point out the difficulty in distinguishing homozygosity for hemoglobin C from hemoglobin C 0-thalassemia in persons with microcytosis; however, several factors suggest that this child and the father were homozygous for hemoglobin C. Although the mother had slight microcytosis (mean corpuscular volume, 78 μm3), she had hemoglobin disease and could not have had classic 0-thalassemia, which to our knowledge has not been reported to modify the genes encoding hemoglobin S or hemoglobin C. Therefore, the child's 0-thalassemia had to have come from the father, who thus had hemoglobin 0-thalassemia. The father's mean corpuscular volume was 67.2 μm3, and high-performance liquid chromatography showed 3.3 percent hemoglobin A2 and 0.6 percent hemoglobin F. Because the father's hemoglobin A2 and F levels were similar to standard reference values and those measured in our laboratory in four unrelated persons from Mali who were homozygous for hemoglobin C (hemoglobin A2, 3.2 to 3.9 percent; hemoglobin F, 0.8 to 1.9 percent) and because hemoglobin F levels range from 3 percent to 10 percent in persons with hemoglobin C 0-thalassemia,1 we believe that the father most likely was homozygous for hemoglobin C. The child's mean corpuscular volume was measured at the age of three months, when -thalassemia would be more apparent than -thalassemia. We do not know the child's hemoglobin A2 value. We speculate that -thalassemia may have contributed to the microcytosis seen in all three family members.
Rick M. Fairhurst, M.D., Ph.D.
National Institute of Allergy and Infectious Diseases
Bethesda, MD 20892
James F. Casella, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
References
Bunn HF, Forget BG. Hemoglobin: molecular, genetic and clinical aspects. Philadelphia: W.B. Saunders, 1986.
Joel G. Schwab, M.D.
Herbert T. Abelson, M.D.
University of Chicago
Chicago, IL 60637
jschwab@peds.bsd.uchicago.edu
References
Fairhurst RM, Casella JF. Homozygous hemoglobin C disease. N Engl J Med 2004;350:e24-e24.
Weatherall DJ, Clegg JB. The thalassaemia syndromes. 4th ed. Oxford, England: Blackwell Science, 2001:415-9.
The authors reply: Drs. Schwab and Abelson point out the difficulty in distinguishing homozygosity for hemoglobin C from hemoglobin C 0-thalassemia in persons with microcytosis; however, several factors suggest that this child and the father were homozygous for hemoglobin C. Although the mother had slight microcytosis (mean corpuscular volume, 78 μm3), she had hemoglobin disease and could not have had classic 0-thalassemia, which to our knowledge has not been reported to modify the genes encoding hemoglobin S or hemoglobin C. Therefore, the child's 0-thalassemia had to have come from the father, who thus had hemoglobin 0-thalassemia. The father's mean corpuscular volume was 67.2 μm3, and high-performance liquid chromatography showed 3.3 percent hemoglobin A2 and 0.6 percent hemoglobin F. Because the father's hemoglobin A2 and F levels were similar to standard reference values and those measured in our laboratory in four unrelated persons from Mali who were homozygous for hemoglobin C (hemoglobin A2, 3.2 to 3.9 percent; hemoglobin F, 0.8 to 1.9 percent) and because hemoglobin F levels range from 3 percent to 10 percent in persons with hemoglobin C 0-thalassemia,1 we believe that the father most likely was homozygous for hemoglobin C. The child's mean corpuscular volume was measured at the age of three months, when -thalassemia would be more apparent than -thalassemia. We do not know the child's hemoglobin A2 value. We speculate that -thalassemia may have contributed to the microcytosis seen in all three family members.
Rick M. Fairhurst, M.D., Ph.D.
National Institute of Allergy and Infectious Diseases
Bethesda, MD 20892
James F. Casella, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
References
Bunn HF, Forget BG. Hemoglobin: molecular, genetic and clinical aspects. Philadelphia: W.B. Saunders, 1986.