Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: A molecular and hematological analysis

Hemoglobin (Hb) C (alpha(2)beta(2)(6Glu-Lys)) is a variant Hb found mainly in West Africa where individuals carrying both Hb C and Hb S (alpha(2)beta(2)(6Glu-Val)) usually have a disease similar to sickle cell disease. The Hb C molecule has reduced solubility leading to crystal formation and hemolytic anemia. We report a hitherto undescribed interaction of Hb C and Hb Malay (alpha(2)beta(2)(19Asn-Ser)) in a Thai individual. She was a 24-year-old pregnant woman with moderate anemia who had the following hematologic data; Hb 8.9 g/dl, Hct 30.0%, MCV 81.0 fl, MCH 24.1 pg, MCHC 29.7 g/dl, RDW 17.1% and instead of Hb crystal a marked number of target cell in peripheral blood was observed. Hb analysis revealed 22.5% Hb Malay, 64.6% Hb C and 4.5% Hb A(2). Globin gene analyses demonstrated that she carried the beta(C) mutation (beta 6: GAG-AAG) in trans to the Malay mutation (beta 19: AAC-AGC). Hematologic data of the patient were compared to those of the compound heterozygote for Hb C and Hb E (alpha(2)beta(2)(26Glu-Lys)) found in 5 other unrelated Thai pregnant women and 11 pregnant women with Hb C heterozygote with or without co-inheritance of alpha-thalassemia who had much lower Hb C levels and the non-pregnant women with Hb C heterozygote and a compound Hb E/Hb Malay syndrome. Different genotype-phenotype correlations observed in these Thai patients with Hb C disorders are illustrated. (c) 2005 Elsevier Inc. All rights reserved.