Thiamine‐responsive myelodysplasia

Bazarbachi, Ali; Muakkit, Samar; Ayas, Mouhab; Taher, Ali T.; Salem, Ziad; Solh, Hassan El; Haidar, Joud H.

doi:10.1046/j.1365-2141.1998.00861.x

Cited by 46 publications

(20 citation statements)

References 7 publications

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“…Thiamine deficiency probably interferes with the high metabolic demand in these cells. Megaloblastic anemia with ring sideroblasts is the most common picture in TRMA (11,27). Thrombocytopenia has been less commonly reported in TRMA patients.…”

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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“…We used the TMPRED program to predict the orientation and location of transmembrane re- Bazarbachi et al, 1998 Previously described mutations: *, Diaz et al, 1999;**, Labay et al, 1999; ***, Fleming et al, 1999. gions, and the ScanProsite program to compare protein sequences and to identify sequence patterns.…”

Section: Computer Analysismentioning

confidence: 99%

“…In addition some patients also have congenital heart anomalies, arrhythmias, and/or abnormalities of the retina. Disease onset is in early childhood, and most of the patients respond to treatment with pharmacological doses of thiamine [Rogers et al, 1969;Viana and Caravalho, 1978;Haworth et al, 1982;Mandel et al, 1984;Borgna-Pignatti et al, 1989;Grill et al, 1991;Vora and Lilleyman, 1993;Rindi et al, 1994;Bazarbachi et al, 1998]. We have recently found mutations in a novel gene, SLC19A2 (MIM# 603941), encoding a putative transmembrane protein homologous to the reduced folate carrier proteins [Labay et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia geneSLC19A2 of eight families

et al. 2000

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“…Iron deficiency impinges on erythrocytic cytoplasm, accompanied by the emergence of erythroblasts with the retention of erythrocytic nuclei. Studies demonstrated the existence of megakaryocytes and ring sideroblasts in the bone marrow of TRMA patients [14], indicating that thiamine deficiency can simultaneously lead to abnormal development in the cytoplasm and nuclei. Thiamine is an important vitamin for humans, and its activated form is thiamine pyrophosphate, which is a coenzyme of transketolase in the phosphate pentose pathway.…”

Section: Discussionmentioning

confidence: 99%

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

Xian

Liao

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. Methods: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1–3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband’s and his brother’s clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband’s whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). Results: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband’s whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.

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Thiamine‐responsive myelodysplasia

Cited by 46 publications

References 7 publications

Thiamine transporter mutation: an example of monogenic diabetes mellitus

Thiamine transporter mutation: an example of monogenic diabetes mellitus

The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia geneSLC19A2 of eight families

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

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