Thiamine responsive megaloblastic anemia syndrome: A novel homozygous <i>SLC19A2</i> gene mutation identified

Mikštienė, Violeta; Songailienė, Jurgita; Byčkova, Jekaterina; Rutkauskienė, Giedrė; Jašinskienė, Edita; Verkauskienė, Rasa; Lesinskas, Eugenijus; Utkus, Algirdas

doi:10.1002/ajmg.a.37015

Cited by 31 publications

(24 citation statements)

References 21 publications

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“…To date, more than 40 different SLC19A2 mutations have been identified in less than 60 families [18][19][20][21][22][23]. The majority of these have been described in individual case reports or small series and the focus has been mainly on the haematological manifestations of the condition.…”

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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Section: Introductionmentioning

confidence: 99%

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

et al. 2018

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“…reported that the clinical condition of a 3-yearold male patient markedly improved several days after the initiation of daily supplementation with thiamine 100 mg. 13 In our case, anemia initially improved with 100 mg/day thiamine treatment. Hemoglobin level increased to 13 g/dl from 7 g/dl after 100 mg/day thiamine treatment.…”

Section: Discussionmentioning

confidence: 47%

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

et al. 2017

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Background. Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case presentation. We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. Conclusion. Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.

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“…TRMA is a rare syndrome, with less than 80 reported cases 8. To our knowledge, this case is the only one described in Switzerland.…”

Section: Discussionmentioning

confidence: 77%

Pancytopenia in an adult patient with thiamine-responsive megaloblastic anaemia

et al. 2018

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Thiamine-responsive megaloblastic anaemia (TRMA) is a syndrome associated with megaloblastic anaemia, diabetes mellitus and sensorineural deafness, due to mutations in the gene, which codes for a thiamine carrier protein. Oral thiamine supplementation is the main treatment. We report the case of a 25-year-old woman known for TRMA, who presented with pancytopenia (haemoglobin 7.6 g/dL, leucocytes 2.9×10/L, thrombocytes 6×10/L) revealed by dyspnoea. Investigations excluded coagulopathy, a recent viral infection, vitamin and iron deficiencies, and a malignant process. We later found out that thiamine treatment had been discontinued 5 weeks before, due to prescription error. Parenteral thiamine administration resulted in the recovery of haematopoiesis within 3 weeks. Pancytopenia is uncommon in patients with TRMA. Pre-existing medullary impairment caused by the patient's daily antipsychotic medications or the natural course of the syndrome may explain the severity of the laboratory findings in our patient.

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Thiamine responsive megaloblastic anemia syndrome: A novel homozygous SLC19A2 gene mutation identified

Cited by 31 publications

References 21 publications

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

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

Pancytopenia in an adult patient with thiamine-responsive megaloblastic anaemia

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