Endocrine Abstracts

Thiamine-Responsive Megaloblastic Anaemia (TRMA) is a rare autosomal recessive disorder emerging due to mutation in the thiamine transporter 1 gene. It presents with sensorineural hearing loss, non-immune diabetes mellitus and megaloblastic anaemia. Ocular manifestations of TRMA described so far include optic atrophy and cone-rod retinal dystrophy. This case-report presents an adolescent British-Pakistani boy with TRMA, who was unexpectedly diagnosed with bilateral severe proliferative retinopathy and macular oedema, just 3 months after being diagnosed with diabetes. His parents are first cousins. He was diagnosed with bilateral sensorineural hearing loss at 2 years of age. He subsequently presented at 14 years of age with mastoiditis, when he was also found to be in diabetic ketoacidosis (DKA). Tests for islet-specific autoantibodies were negative. First retinal screening (3 months after presentation with DKA) identified bilateral high-risk proliferative retinopathy and macular oedema. At the same time, he was admitted with breathing difficulty and was found to have anaemia, thrombocytopaenia and reticulocytopaenia. Peripheral smear demonstrated marked poikilocytosis. Further evaluation for pancytopenia revealed normal clotting, lactate dehydrogenase, vitamin B12, folic acid and ADAMTS-13 levels and test results for autoantibodies and PCR for several viruses were negative. Bone marrow examination revealed erythroid dysplasia and numerous ring sideroblasts, and this eventually led to the diagnosis of TRMA. Red-cell thiamine level was 60 nmol/l (67–200). He was started on high-dose thiamine therapy (50 mg/day). Haemoglobin, red cell and platelet count improved and normalised within 3 weeks. Red-cell MCV increased from 79.9 to 100 fL. The patient is homozygous for a pathogenic SLC19A2 nonsense variant NM_006996.2:c.196G>T p. (Glu66Ter) and both parents are heterozygous for the same mutation. He has had pan-retinal photocoagulation and his diabetes is better controlled since starting thiamine, though he continues to require insulin therapy. Proliferative retinopathy within 3 months of diabetes diagnosis in adolescence, is highly unusual. It may be due to the combined effect of intracellular thiamine deficiency and severe hyperglycaemia.