TRMA Is caused by homozygous mutation in the SLC19A2 gene, which encodes a thiamine transporter protein, on chromosome 1q24
TRMA is characterized by the phenotypic triad of a) megaloblastic anemia, b) sensorineural hearing loss, and c) diabetes mellitus. Onset of megaloblastic anemia is between infancy and adolescence..Examination of the bone marrow reveals megaloblastic anemia with erythroblasts often containing iron-filled mitochondria (ringed sideroblasts).
Treatment of TRMA focuses on lifelong use of pharmacologic doses (25-75 mg/day) of thiamine (vitamin B1). With this, anemia is corrected but, the red cells remain macrocytic. Moreover, anemia can recur when thiamine is withdrawn
TRMA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible for families in which the pathogenic variants have been identified.