Enabling routine β-Thalassemia Prevention and Patient Management by Scalable, Combined Thalassemia and Hemochromatosis Mutation Analysis

Abstract Abstract: Background : Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past 40 years, many countries have implemented awareness and prevention campaigns that have greatly reduced the incidence of affected child births. In contrast, much remains to be done in South-Asia. Thus, for Pakistan, current estimates of the number of children born with thalassemia are at ~7,000 per annum, with no sign of improvement. Although there is good agreement that intermarriage of carriers is a principal source of the high prevalence of the disorder, effective tools for screening and diagnosis on which to base prevention programs are not readily available. Methods : Here, we present results for a novel “LeanSequencing” process to identify 18 β-thalassemia and related sickle cell anemia, and simultaneously a set of 3 hemochromatosis mutations in a multi-ethnic population of 274 pediatric and adolescent patients treated at Afzaal Memorial Thalassemia Foundation hospital in Karachi, Pakistan. Results : We found substantial differences in the abundance of disease-causing mutations among the principal ethnic groups in our cohort. We also found the hemochromatosis mutation H63D C > G in 61 (or 22.1%) of our patients including 7 (or 2.6%) homozygotes. Conclusions : To our knowledge, this is the first screen combining β-thalassemia and hemochromatosis mutations in a single test, so as to facilitate the early identification of patients who may be at increased potential risk for complications from iron overload and thereby to improve the prospective management of thalassemia patients.