Thiamine-responsive megaloblastic anemia syndrome: A disorder of high-affinity thiamine transport

Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) comprises a distinctive triad of clinical features: megaloblastic anemia wi th ringed sideroblasts, diabetes mellitus, and progressive sensorineural de afness. The TRMA gene has been mapped and cloned. Designated "SLC19A2" as a member of the solute carrier gene superfamily, this gene is mutated in all TRMA kindreds studied to date. The product of the SLC19A2 gene is a membra ne protein which transports thiamine (vitamin BI) with sub-micromolar affin ity. Cells from TRMA patients are uniquely sensitive to thiamine depletion to the nanomolar range, while pharmacologic doses of vitamin B1 ameliorate the anemia and diabetes. Here we review the current status of studies aimed at understanding the pathophysiology of this unique transport defect, (C) 2001 Academic Press.