title: Thiamine transporter mutation: an example of monogenic diabetes mellitus.
abstract: OBJECTIVE
  Thiamine-responsive megaloblastic anemia (TRMA) is a rare syndrome characterized by diabetes mellitus (DM), anemia, and sensorineural deafness. We describe the clinical course and the molecular defect of a young woman who was diagnosed to have this syndrome.
  
  
  METHODS
  The patient is an 18-year-old girl who was born to non-consanguous parents. She was noted to be deaf-mute in the first year of life. She was diagnosed with DM at the age of 9 months and with severe anemia at the age of 2 years. An extensive work up could not identify the cause. She was treated with blood transfusions every 3-4 weeks for the past 16 years. A diagnosis of TRMA was suspected and the patient was treated with thiamine hydrochloride. Hemoglobin and platelets increased to normal values after a few weeks of thiamine therapy. Diabetic control significantly improved but she had no noticeable changes in the deafness.
  
  
  METHODS
  Peripheral blood DNA was extracted from the patient, her mother, aunt, and a healthy sister. Exons and exon-intron boundaries of the thiamine transporter gene SLC19A2 were PCR amplified and directly sequenced.
  
  
  RESULTS
  A G515C homozygous mutation was identified in the SLC19A2 gene of the patient. This mutation changes Gly to Arg at codon 172 (G172R). The mother, an aunt, and a sister had a heterozygous G172R mutation.
  
  
  CONCLUSIONS
  Mutations in thiamine transporter gene, SLC19A2, causes a rare form of monogenic diabetes, anemia, and sensorineural deafness. Thiamine induces a remarkable hematological response and improvement in the diabetic control but has no effect on deafness.
authors.affiliation: Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. aliz@kfshrc.edu.sa
authors.forename: Ali S
authors.initials: AS
authors.lastname: Alzahrani
authors.forename: Essa
authors.initials: E
authors.lastname: Baitei
authors.forename: Minging
authors.initials: M
authors.lastname: Zou
authors.forename: Yufei
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000749:Anemia, Megaloblastic / Q000188:drug therapy / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D017354:Point Mutation; D013831:Thiamine / Q000378:metabolism / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D014803:Vitamin B Complex; D013831:Thiamine