Abstrakt
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/.