Genetic Basis of Thalassemia Syndromes: Implications to Reduce Disease Burden

Thalassemia syndromes constitute the commonest monogenic disorders in Indians and inheritance is autosomal recessive. Conservative estimates are >10,000 new cases/year of thalassemia major (TM) are born in India and this poses a considerable burden to the health care system. Parents of TM are carriers (beta thalassemia trait; [beta]TT) and they constitute the asymptomatic reservoir of the disease. Identifying the spectrum of beta mutations in different regions has shown considerable heterogeneity. Approximately 70 beta mutations have been found in Indians but 6-7 mutations constitute 80-90%. Though IVS 1-5 G [right arrow] C is the commonest mutation encountered, the frequency varies from 15 to 88% in different states. Fr 41/42 (-CTTT) is also widely encountered but commoner in the north. Increasing the awareness amongst the doctors, health professionals and general public will go a long way in reducing the prevalence of TM by widespread antenatal screening programs and cascade screening. Majority of the carriers can be identified by analyzing the automated blood cell counter reports. Hypochromic microcytosis ([down arrow]MCV and MCH) and relative erythrocytosis ([up arrow] RBC counts) are found in [beta]TT's. Increased HbA2 fraction of >4% on HPLC quantitation is the diagnostic hallmark of identifying carriers. Prompt screening of the husbands from the antenatal clinics and offering prenatal diagnosis should be done. For mutational characterization, ARMS-PCR is most widely applied followed by RDB analysis. Occasionally with rare mutations beta gene sequencing is done. All prenatal centres should perform chorionic villous biopsy/ amniocentesis. Maternal contamination should be excluded using VNTR or STR analysis. Presently about 10 centres are offering prenatal diagnosis. Constant training programs to increase the manpower to perform screening and prenatal diagnosis are the need of the hour. Involvement of the State and Central Government is required to combat this potentially preventable genetic disorder on an urgent basis.