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

Blood Cells Mol Dis. Jan-Feb 2001;27(1):135-8. doi: 10.1006/bcmd.2000.0356.

Abstract

Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) comprises a distinctive triad of clinical features: megaloblastic anemia with ringed sideroblasts, diabetes mellitus, and progressive sensorineural deafness. 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 membrane protein which transports thiamine (vitamin B1) with sub-micromolar affinity. 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.

Publication types

  • Review

MeSH terms

  • Anemia, Megaloblastic / epidemiology
  • Anemia, Megaloblastic / etiology
  • Anemia, Megaloblastic / genetics*
  • Animals
  • Carrier Proteins / genetics*
  • Genotype
  • Humans
  • Membrane Transport Proteins*
  • Mutation
  • Syndrome
  • Thiamine / pharmacology

Substances

  • Carrier Proteins
  • Membrane Transport Proteins
  • SLC19A2 protein, human
  • Thiamine