We studied the alpha-globin gene abnormalities, the clinical features, hematologic values, growth assessment, transfusion therapy, and serum ferritin levels of patients with hemoglobin H (HbH) disease in southern Thailand. HbH disease in 83 of the 147 patients was the deletional type of HbH. The remaining 64 patients was the nondeletional type of HbH disease. All 83 patients with the deletional type were double heterozygotes of alpha(0)-thalassemia and alpha(+)-thalassemia. The Southeast Asian type of alpha(0)-thalassemia accounted for 98% of the Thai patients with HbH disease and the Thai type of alpha(0)-thalassemia made up the rest. A 3.7-kb deletion accounted for 91% of alpha(+)-thalassemia, and a 4.2-kb deletion made up the rest of the deletional type. In patients with nondeletional type of HbH disease, the Constant Spring variant was the majority of the disease. Newborns with a nondeletional genotype had higher mean corpuscular volume, had higher mean corpuscular hemoglobin, had higher red blood cell distribution width, had lower mean corpuscular hemoglobin concentration, and had higher proportions of Hb Bart's than those with a deletional genotype. Twenty-one percent of children with HbH disease had growth deficiency. A genotype-phenotype correlation was found; patients with the nondeletional type of HbH disease had more symptoms at a younger age, more severe hemolytic anemia, more growth deficiency, more dysmorphic facial features, larger spleens, larger livers, and higher serum ferritin levels and required more transfusions than patients with deletional HbH disease.

In this report, we describe two Thai siblings presenting with mild hypochromic microcytic anaemia and splenomegaly since 2(1/2) years of age. However, both patients were otherwise well with normal weight and height development and did not require transfusion during the 6-year follow-up period. Haematological and haemoglobin analyses were consistent with the clinical diagnosis of Hb E/beta-thalassaemia disease. To provide proper genetic counselling for this family, a definitive diagnosis of beta-thalassaemia was achieved using molecular analysis. We identified a rare initiation codon mutation (ATG-->AGG) of the beta-globin gene in combination with the Hb E mutation (codon 26: GAG-->AAG). The initiation codon mutation has previously been reported in several East Asian populations but has never been found in Southeast Asia and in combination with Hb E before. The haplotype analysis revealed a common origin of this mutation in the Asian population (5': - + - + + - +: 3', type IV with framework 3 according to Orkin S, et al.). Although this rare mutation abolished the beta-globin expression and was considered as beta(0)-thalassaemia, the relatively mild phenotype in our patients may be attributed to a strong association between this mutation and the -158 (G)gamma (C-->T) polymorphism, an XmnI cleavage site (+), resulting in a high propensity of postnatal gamma-globin expression and ameliorating the clinical phenotypes.