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.

CASE:

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: Ali S Alzahrani, Essa Baitei, Minging Zou, Yufei Shi
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 155 Issue 6 Pg. 787-92 (Dec 2006) ISSN: 0804-4643 [Print] England
• PMID: 17132746 (Publication Type: Case Reports, Journal Article)

Chemical References

• Membrane Transport Proteins
• SLC19A2 protein, human
• Vitamin B Complex
• Thiamine

Topics

• Adolescent
• Anemia, Megaloblastic (drug therapy, genetics)
• Diabetes Mellitus, Type 1 (drug therapy, genetics)
• Female
• Hearing Loss, Sensorineural (genetics)
• Humans
• Membrane Transport Proteins (genetics)
• Point Mutation
• Thiamine (metabolism, therapeutic use)
• Vitamin B Complex (metabolism, therapeutic use)