Effect of management of thiamine responsive megaloblastic anemia syndrome with sulbutiamine

Abstract

Introduction: thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare autosomal recessive metabolic disorder. Management of TRMAS focuses on lifelong use of pharmacologic doses of thiamine (Th). High-dose Th may ameliorate diabetes, anemia and, conjecture, hearing defect if started from birth or prenatally. TRMAS management with Th hydrochloride and Benfotiamine, a synthetic Th analog, has been described. Effect of lipophilic synthetic thiamine derivate, sulbutiamine, effectively crossing blood-brain barrier and possessing good bioavailability, has never been published. Materials and methods: we report a 6y old boy clinically and molecularly diagnosed with TRMAS at the age of 3y. Thiamine 100mg/day was administered. The condition markedly improved several days after the initiation of treatment - therapy had positive effect on anemia and glycaemia, also psychological status of the child slightly improved. After several months the patient developed allergic reaction. Moreover, the effect of thiamine was not sufficient for timely mental development and psychological balance. After careful consideration thiamine was replaced with sulbutiamine 100mg/day. Results: we observed transitory decrease of hemoglobin to 110g/l which resolved within 1st month of treatment. Blood glycaemia remained stable, with rare elevations due to stress. Unfortunately, 1 year of treatment with sulbutiamine did not improve the patient’s mental health: emotional outbursts, aggressive behavior, speech delay, and inability to address hygiene tasks remain. Conclusions: our experience demonstrate that sulbutiamine benefits in maintenance of blood glycaemia and hematopoiesis in TRMAS patient. The expected improvement of mental performance was not attained supposedly due to the late diagnosis or possible additional underlying condition.