Thiamine‐responsive megaloblastic anaemia syndrome: Long‐term follow‐up and mutation analysis of seven families

Ricketts, Christopher J.; Minton, Jayne A.L.; Samuel, Jacob; Ariyawansa, Indra; Wales, Jerry; Lo, Ivan F. M.; Barrett, Timothy

doi:10.1111/j.1651-2227.2006.tb02188.x

Cited by 23 publications

(32 citation statements)

References 21 publications

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“…In 1978, a second case was reported by Viana & Carvalho (7). Since then, a number of cases have been described (4,(8)(9)(10)(11)(12)(13). It was postulated that this syndrome is related to defects in thiamine metabolism (1,7,14).…”

Section: Discussionmentioning

confidence: 99%

Thiamine transporter mutation: an example of monogenic diabetes mellitus

Alzahrani

Baitei²,

Zou³

et al. 2006

eur j endocrinol

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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

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Section: Discussionmentioning

confidence: 99%

Thiamine transporter mutation: an example of monogenic diabetes mellitus

Alzahrani

Baitei²,

Zou³

et al. 2006

eur j endocrinol

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“…In some individuals additional features such as thrombocytopenia, neurological symptoms, cardiac anomalies, visual disturbances and short stature have also been reported [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

et al. 2018

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Aims/hypothesis Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B 1 ) in a cohort of individuals with TRMA-related diabetes. Methods We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire.Results We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes onset was 10 months . At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Followup data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine (p = 0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and A list of the members of the International Neonatal Diabetes Consortium is included in the electronic supplementary material (ESM).Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-018-4554-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…Literatürde, baş-langıçta tiamine yanıt veren aneminin özellikle erişkin dönemlerde transfüzyon bağımlı olabileceği bildirilmiştir. 5 Olgumuzun altı aylık izleminde hemoglobin değerinde düşüş olmadı, ancak bu açıdan izlenmeye devam edilmektedir.…”

Section: Discussionunclassified

“…Diyabet kliniği sık-lıkla okul öncesi dönemde olmak üzere yaşamın herhangi bir döneminde ortaya çıkabilmektedir. 5,10 Diabetes mellitus tiamin tedavisine yanıt vermektedir. Ancak, uzun dönem izlenen hastalarda pubertal dönemde insülin ihtiyacı olabileceği bildirilmiştir.…”

Section: Discussionunclassified