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 deafmute 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 DNAwas 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.European Journal of Endocrinology 155 787-792

Thiamine Prevents Obesity and Obesity-Associated Metabolic Disorders in OLETF Rats

“…Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an earlyonset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, which responds to thiamine treatment in varying degrees. TRMA is a rare genetic disorder in which diabetes, other than type 1 diabetes mellitus, is secondary to a single gene disorder, a thiamine transporter defect (11)(12)(13)(14). Type 2 diabetes mellitus has been linked to the chromosome 1q23.…”

Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report

“…3,5 Alzahrani et al informed that high dose thiamine therapy in TRMA patients can improve the disease symptoms, correct the anemia and reduce or discontinue the need for exogenous insulin. 12 Our patient was diagnosed non-autoimmune diabetes mellitus at age of 3 months. Diabetes mellitus in TRMA is a non-autoimmune disorder due to a defect of insulin secretion.…”

Síndrome de anemia megaloblástica sensible a la tiamina de aparición en la niñez, con mutación en el gen SLC19A2: caso clínico

“…12 En el caso de la paciente que presentamos, se le diagnosticó diabetes mellitus no autoinmunitaria a la edad de 3 meses. La diabetes mellitus en pacientes con TRMA es un trastorno no autoinmunitario debido a un defecto en la secreción de insulina.…”