Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings

Mozzillo E, Melis D, Falco M, Fattorusso V, Taurisano R, Flanagan SE,Ellard S, Franzese A. Thiamine responsive megaloblastic anemia: a novelSLC19A2 compound heterozygous mutation in two siblings.Pediatric Diabetes 2013: 14: 384–387.Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessivedisease caused by loss of function mutations in the SLC19A2 gene. TRMA ischaracterized by anemia, deafness, and diabetes. In some cases, optic atrophyor more rarely retinitis pigmentosa is noted. We now report two sisters, theeldest of which presented to a different hospital during childhood withsensorineural deafness, which was treated with a hearing prosthesis, insulinrequiring diabetes, retinitis pigmentosa, optic atrophy, and macrocyticanemia. These features initially suggested a clinical diagnosis of Wolframsyndrome (WS). Therapy with thiamine was initiated which resulted in theresolution of the anemia. The younger sister, who was affected withsensorineural deafness, was referred to our hospital for non-autoimmunediabetes. She was found to have macrocytosis and ocular abnormalities.Because a diagnosis of TRMA was suspected, therapy with insulin andthiamine was started. Sequencing analysis of the SLC19A2 gene identified acompound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT)in both sisters. Non-autoimmune diabetes associated with deafness andmacrocytosis, without anemia, suggests a diagnosis of TRMA. Patientsclinically diagnosed with WS with anemia and/or macrocytosis should bereevaluated for TRMA.