TRMA syndrome [thiamine-responsive megaloblastic anaemia syndrome, OMIM#249270] is associated with the classic clinical triad of diabetes, deafness, and megaloblastic anaemia. Diabetes in this condition typically occurs in infancy but has been reported in association with neonatal diabetes in rare cases. Other additional features which may be observed in affected individuals include congenital heart malformations, tri-lineage myelodysplasia, and visual issues such as optic atrophy or retinitis pigmentosa.
Homozygous or compounded heterozygous mutations in the SLC19A2 gene [OMIM#603941] are associated with TRMA. SLC19A2 encodes a high-affinity thiamine transporter, and studies on the fibroblasts of affected individuals have shown that absence of this transporter protein results in low intracellular thiamine levels. The mechanism by which absence of this protein leads to the divergent symptoms associated with TRMA remains unknown.