HB-SUN-PRAIRIE - DIAGNOSTIC PITFALLS IN THALASSEMIC HEMOGLOBINOPATHIES

We report an Asian Indian family in which two daughters have Hb Sun Pr airie, a known unstable alpha 2-globin variant [codon 130, <(G)under b ar CT>--><(C)under bar CT> alpha(2)130(H13)Ala-->Pro beta(2)]. While t he homozygous probands have chronic hemolysis - the same phenotype as previously reported, the heterozygous parents are asymptomatic with a thalassemia carrier phenotype, distinct from the chronic hemolytic sta te previously described in a heterozygote. Unlike the earlier cases in which family studies were not available, this family clearly exhibits autosomal recessive inheritance, unusual amongst variants within the same region of helix H. Globin chain biosynthesis ratios initially sug gested a beta-thalassemic hemoglobinopathy - this was excluded by norm al sequence analysis of both beta-globin genes. This case report furth er illustrates the complexity of phenotypes in the thalassemic hemoglo binopathies. It also demonstrates inversion of the alpha/beta-globin c hain biosynthesis ratio, a phenomenon which had been noted in other al pha-globin variants and can be a confounding factor in the investigati on of thalassemic hemoglobinopathies.