A novel homozygous SLC19A2 mutation in a Portuguese patient with diabetes mellitus and thiamine-responsive megaloblastic anaemia

Tahir, Sophia; Leijssen, Lieve G.J.; Sherif, Maha; Pereira, Carla; Morais, Anabela; Hussain, Khalid

doi:10.1186/s13633-015-0002-6

Cited by 15 publications

(24 citation statements)

References 27 publications

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“…TRMA has been reported in less than 80 cases worldwide . To date at least 43 mutations have been described in the SLC19A2 gene . However, the number of European cases is even lower …”

Section: Introductionmentioning

confidence: 84%

“…A high concentration of thiamine plays an essential role in carbohydrate metabolism and energy production reactions. Reduced intracellular thiamine concentration leads to apoptosis of the cells . Thiamine is transported by 2 high affinity carriers found in the intestine—THTR‐1 encoded by the SLC19A2 gene and THTR‐2 encoded by the SLC19A3 gene.…”

Section: Introductionmentioning

confidence: 99%

“…In TRMA, most cells have compensatory mechanism via THTR‐2. Only the 3 THTR‐1 dependent cells are the most affected by thiamine deficiency . The treatment of TRMA includes thiamine supplementation, which may correct hematological and endocrine function …”

Section: Introductionmentioning

confidence: 99%

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First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G

et al. 2016

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Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.

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“…TRMA has been reported in less than 80 cases worldwide . To date at least 43 mutations have been described in the SLC19A2 gene . However, the number of European cases is even lower …”

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G

et al. 2016

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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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“…4,27,[56][57][58][59] Although mutations in SLC19A2 are one of the causes of PNDM, 1 the clinical diagnosis of SLC19A2 deficiency is rarely made until the presentation of all syndromic symptoms (i.e. diabetes, anemia, and deafness) and is sometimes unrecognized among patients with early onset diabetes.…”

Section: Discussionmentioning

confidence: 99%

Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation

Sun

Zhou

Zhang

et al. 2017

Journal of Diabetes

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Background: Solute carrier family 19 member 2 (SLC19A2) gene deficiency is one of the causes of permanent neonatal diabetes mellitus (PNDM) and can be effectively managed by thiamine supplementation. Herein we report on a male patient with a novel SLC19A2 mutation and summarize the clinical characteristics of patients with SLC19A2 deficiency. Methods: The genetic diagnosis of the patient with PNDM was made by sequencing and quantitative polymerase chain reaction. The clinical characteristics of PNDM were summarized on the basis of a systematic review of the literature. Results: The patient with PNDM had c.848G>A (p.W283X) homozygous mutation in SLC19A2. His father had a wild-type SLC19A2 (c.848G) and his mother was c.848G/A heterozygous. The patient and his father both had a diploid genotype (c.848A/A and c.848G/G). After oral thiamine administration, the patient's fasting C-peptide levels increased gradually, and there was a marked decrease in insulin requirements. A search of the literature revealed that thiamine treatment was effective and improved diabetes in 63% of patients with SLC19A2 deficiency. Conclusions: A novel SLC19A2 mutation (c.848G>A; p.W283X) was identified, which was most likely inherited as segmental uniparental isodisomy. Insulin insufficiency in PNDM caused by SLC19A2 deficiency can be corrected by thiamine supplementation. The differential diagnosis of SLC19A2 deficiency should be considered in children with PNDM accompanied by anemia or hearing defects to allow for early treatment.

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A novel homozygous SLC19A2 mutation in a Portuguese patient with diabetes mellitus and thiamine-responsive megaloblastic anaemia

Cited by 15 publications

References 27 publications

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation

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