Endocrine Abstracts

A 5-year-old girl transferred into our service with antibody negative diabetes (to islet antigen 2 and glutamic acid), diagnosed aged 15 months, following a 4-week history of polyuria and polydipsia, without diabetic ketoacidosis (C-peptide (CP) 576 pmol/l and presenting glucose 14 mmol/l). She was treated with multiple daily injections from diagnosis. There was a history of severe progressive sensorineural deafness since six months, and iron deficiency normocytic anaemia. Genetic testing was negative for the deafness panel R67, which includes Wolfram syndrome (diabetes mellitus, diabetes insipidus, optic atrophy, and deafness). The family were of Pakistani ethnicity, and parents were first cousins. Given the history of syndromic antibody negative diabetes, further genetic testing was sent for the R153 panel (Exeter genetics laboratory), confirming the diagnosis of Thiamine-responsive megaloblastic anaemia (Rogers syndrome). This is a rare autosomal recessive condition, comprising one or more features of megaloblastic anaemia, diabetes mellitus and sensorineural deafness. The phenotype is due to a loss of function mutation of SLC19A2, encoding for high affinity thiamine transporter 1, the main thiamine transporter expressed in haematopoietic stem cells, pancreatic beta cells and inner ear cells. Thiamine is essential for beta cell function and a co-factor for other intracellular enzymes. Absence of the transporter means thiamine cannot be transported into the cells at physiological levels. Treatment at higher concentrations allows thiamine to cross cell membranes by diffusion. After 7 weeks of titrating oral thiamine (100 mg once daily), there was a reduction in insulin dose (0.71 units/kg/day baseline, 0.58 units/kg/day at 7 weeks) and a resolution in hypoglycaemia without a deterioration in Haemoglobin A1c (58 mmol/mol). This mirrored an improvement in pancreatic CP production (CP, baseline: 7 pmol/l, 497 pmol/l at 7 weeks). Further dose titration is ongoing. We propose that SLC19A2 is added to the deafness panel, to allow a prompt diagnosis. Thiamine treatment is most effective as early as possible, to reduce or reverse insulin requirement. In this case, even after a 3-year delay in thiamine treatment, there was a clinically meaningful treatment response. This case highlights the importance of remaining clinically curious, even in the context of reassuring pre-existing genetic tests.