Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome

Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome Publisher Pubmed

Habeb AM¹ ; Flanagan SE² ; Zulali MA³ ; Abdullah MA⁴ ; Pomahacova R⁵ ; Boyadzhiev V⁶ ; Colindres LE⁷ ; Godoy GV⁷ ; Vasanthi T⁸ ; Al Saif R⁹ ; Setoodeh A¹⁰ ; Haghighi A¹¹ ; Haghighi A¹¹ ; Shaalan Y¹⁵ Show All Authors

Habeb AM¹
Flanagan SE²
Zulali MA³
Abdullah MA⁴
Pomahacova R⁵
Boyadzhiev V⁶
Colindres LE⁷
Godoy GV⁷
Vasanthi T⁸
Al Saif R⁹
Setoodeh A¹⁰
Haghighi A¹¹
Haghighi A¹¹
Shaalan Y¹⁵
Hattersley AT²
Ellard S²
De Franco E²

Show Affiliations

1. Paediatric Department, Prince Mohammed bin Abdulaziz Hospital, National Guard Ministry, P.O. Box 40740, Al Madinah, 41511, Saudi Arabia
2. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, United Kingdom
3. Paediatric Department, College of Medicine, Taibah University, Madinah, Saudi Arabia
4. Paediatric Department, Khartoum University, Khartoum, Sudan
5. Department of Paediatrics, Charles University, Medical Faculty and University Hospital Pilsen, Pilsen, Czech Republic
6. Medical University, Varna, Bulgaria
7. Hospital Maria De Especialidades Pediatricas, Tegucigalpa, Honduras
8. Kanchi Kamakoh Child Trust Hospital, Chennai, India
9. Paediatric Department, Maternity and Childrenâ€™s Hospital, Dammam, Saudi Arabia
10. Growth & Development Research Centre, University of Tehran, Medical Sciences, Tehran, Iran
11. Toronto General Hospital, University of Toronto, Toronto, ON, Canada
12. Department of Genetics and Medicine, Harvard Medical School, Boston, MA, United States
13. Broad Institutes of Harvard and MIT, Cambridge, MA, United States
14. Partners HealthCare Laboratory for Molecular Medicine, Cambridge, MA, United States
15. Faculty of Medicine, Cairo University, Cairo, Egypt

Source: Diabetologia Published:2018

Abstract

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 B1) 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 (IQR 5–27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up 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 adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day. Conclusions/interpretation: In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent. Data availability: SLC19A2 mutation details have been deposited in the Decipher database (https://decipher.sanger.ac.uk/). © 2018, The Author(s).

2. Recurrent Stroke in a Child With Trma Syndrome and Slc19a2 Gene Mutation, Iranian Journal of Child Neurology (2018)

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Fatemeh Sayarifard (1)

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Style	Citing Format
MLA	Habeb AM, et al.. "Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome." Diabetologia, vol. 61, no. 5, 2018, pp. 1027-1036.
APA	Habeb AM, Flanagan SE, Zulali MA, Abdullah MA, Pomahacova R, Boyadzhiev V, Colindres LE, Godoy GV, Vasanthi T, Al Saif R, Setoodeh A, Haghighi A, Haghighi A, Shaalan Y, Hattersley AT, Ellard S, De Franco E (2018). Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome. Diabetologia, 61(5), 1027-1036.
Chicago	Habeb AM, Flanagan SE, Zulali MA, Abdullah MA, Pomahacova R, Boyadzhiev V, Colindres LE, et al.. "Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome." Diabetologia 61, no. 5 (2018): 1027-1036.
Harvard	Habeb AM et al. (2018) 'Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome', Diabetologia, 61(5), pp. 1027-1036.
Vancouver	Habeb AM, Flanagan SE, Zulali MA, Abdullah MA, Pomahacova R, Boyadzhiev V, et al.. Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome. Diabetologia. 2018;61(5):1027-1036.
BibTex	@article{ author = {Habeb AM and Flanagan SE and Zulali MA and Abdullah MA and Pomahacova R and Boyadzhiev V and Colindres LE and Godoy GV and Vasanthi T and Al Saif R and Setoodeh A and Haghighi A and Haghighi A and Shaalan Y and Hattersley AT and Ellard S and De Franco E}, title = {Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome}, journal = {Diabetologia}, volume = {61}, number = {5}, pages = {1027-1036}, year = {2018} }
RIS	TY - JOUR AU - Habeb AM AU - Flanagan SE AU - Zulali MA AU - Abdullah MA AU - Pomahacova R AU - Boyadzhiev V AU - Colindres LE AU - Godoy GV AU - Vasanthi T AU - Al Saif R AU - Setoodeh A AU - Haghighi A AU - Haghighi A AU - Shaalan Y AU - Hattersley AT AU - Ellard S AU - De Franco E TI - Pharmacogenomics in Diabetes: Outcomes of Thiamine Therapy in Trma Syndrome JO - Diabetologia VL - 61 IS - 5 SP - 1027 EP - 1036 PY - 2018 ER -

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