ESPE Abstracts

Introduction: Wolfram syndrome (WS) is a rare progressive neurodegenerative disease that shows autosomal recessive inheritance characterized by diabetes insipidus, diabetes mellitus (DM), optic nerve atrophy and deafness. WFS1 gene encoding a protein, wolframin, which is essential to the function of the endoplasmic reticulum, is identified as main causative gene of the disease. We report here a sibling case suspected WS with insulin-dependent DM and optic atrophy in early childhood.

Case 1: A 7-year-old boy with no family history of DM and eye disease was referred to our hospital for a positive glucose urine test in elementary school and hyperglycemia. He showed mild diabetic ketoacidosis (DKA). Postprandial glucose and HbA1c levels were 11.8 mmol/l and 10.7%, respectively. Autoantibodies to GAD, insulin, IA-2 and ZnT8 were all negative. The peak C-peptide reactivity (CPR) level after glucagon stimulation was low as 1.32 ng/ml (normal:>3) and he was treated with multiple daily injection of insulin. On an ophthalmologic examination after the diagnosis of DM, atrophy of his optic nerve was revealed.

Case 2; younger brother of Case 1: After two-month episode of nocturnal enuresis at the age of 5 years and 8 months, he showed hyperglycemia of almost 10–20 mmol/l measured by his mother using his brother’s blood glucose meter. It was only 10 months after his brother’s diagnosis of DM. Postprandial glucose and HbA1c levels were 11.8 mmol/l and 9.5%, respectively. Any islet associated autoantibodies were negative. The peak CPR level after glucagon stimulation was 2.73 ng/ml and multiple daily injection of insulin was started. He was also pointed out mild optic atrophy by an ophthalmologic examination.

Discussion/Conclusions: WS was not suspected at first when Case 1 developed insulin-dependent DM. But only after 10 months, his brother also presented insulin-dependent DM without autoimmune response in addition to optic atrophy, so WS was strongly suspected. It is common that DM is the first symptom of WS patients diagnosed around at 10 years old, and other abnormal symptoms occur subsequently. At the moment, they do not show achromatopsia, visual acuity lowering, diabetes insipidus and other neurological or psychiatric symptoms. But since symptoms of WS are progressive, careful observation and follow-up of the patients are needed to note onset rapidly. Genetic diagnosis of WS may be important for the choice of appropriate treatment, the welfare improvement of the patients and the development of future therapy.