Molecular and clinical features of Hb H disease in northern Thailand

Clinical assessment, hematological studies and molecular analyses were performed in 102 pediatric patients with Hb H disease in northern Thailand. A total of six mutations of the alpha-globin gene, which produced five genotypes, were detected. All patients had an alpha(0)-thalassemia (thal) deletion on one chromosome 16. All but one of these were of the South East Asian type (--SEA); one patient had the THAI deletion (--THAI). The deletional alpha(+)-thal mutations comprised 3.7 kb (-alpha(3.70) and 4.2 kb (-alpha(4.2)) deletions which were found in 34 (33.3%) and 10 (9.8%) alleles, respectively. The nondeletional alpha(+)-thal mutations comprised 55 (53.9%) alleles of Hb Constant Spring (CS) (alpha142, TAA --> CAA) and three (2.9%) alleles of Hb Pakse (alpha142, TAA --> TAT). Six patients with Hb H-CS disease also carried Hb E (AEBart's CS disease). The clinical features were diverse and the nondeletional genotypes were associated with more severe clinical and hematological features, including younger age at presentation, larger size of liver and spleen, lower hemoglobin (Hb) level, and higher transfusion requirements. The high proportion of nondeletional Hb H disease observed in this study was inconsistent with the previously reported gene frequencies of alpha-thal in the region, suggesting that many deletional Hb H patients with milder symptoms may have escaped recognition.