Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F18%3A10374863" target="_blank" >RIV/00216208:11140/18:10374863 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00669806:_____/18:10374863

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00125-018-4554-x" target="_blank" >http://dx.doi.org/10.1007/s00125-018-4554-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00125-018-4554-x" target="_blank" >10.1007/s00125-018-4554-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

Popis výsledku v původním jazyce

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. We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. 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 presentations, 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 transtusion-independent and thiamine transporter in these three tissues and explains the presence of deafness, diabetes and anaemia in individuals with TRMA syndrome /10-13/.

Název v anglickém jazyce

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

Popis výsledku anglicky

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. We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. 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 presentations, 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 transtusion-independent and thiamine transporter in these three tissues and explains the presence of deafness, diabetes and anaemia in individuals with TRMA syndrome /10-13/.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Diabetologia

ISSN

0012-186X

e-ISSN

—

Svazek periodika

61

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

1027-1036

Kód UT WoS článku

000428796200005

EID výsledku v databázi Scopus

2-s2.0-85042135078