Clinical phenotypes and molecular diagnosis in a hitherto interaction of Hb E/β thalassemia syndrome (β^E/ β^{-31, A→G})

Abstract

Molecular identification of affected alleles in the index family with rare mutation(s) and/or interaction(s) is an important prerequisite toward a proper genetic counseling. In Thailand, where more than 30% of the populations are heterozygotes for either α or β thalassemia mutation(s). More than 60 different thalassemia syndromes resulting from the interactions of these heterogeneous alleles have been observed.(1) The majority of patients in the hospital based-study are compound heterozygotes for β thalassemia alleles and another hemoglobinopathy namely Hb E, highly prevalent in Thailand, gave rise to Hb E/β thalassemia syndrome. The phenotypes of these syndromes vary from asymptomatic individual to a very severe phenotype mimic that of β thalassemia major. In this report, we describe a three-year-old Thai girl presenting with mild hypochromic microcytic anemia since birth. She was born prematurely and developed anemia within the first week of life. The cause of anemia was suspected to result from prematurity and low intrauterine iron storage, however hypochromic anemia did not resolve after a three-month of iron supplement therapy. Subsequent studies indicated that the patient had Hb E/β thalassemia disease and the molecular study revealed that the patient was a compound heterozygote for Hb E and a rare β+thalassemia mutation (β-31, A→G). This hitherto genotype results in a relatively mild clinical symptom since the patient's baseline Hb values were around 9-10 g/dL with normal weight and height development during the follow-up period.