Endocrine Abstracts

JOINT1602

Introduction: Wolfram syndrome is a rare progressive neurodegenerative disorder caused by a recessive mutation in the WFS1 or WFS2 gene, typically characterized by diabetes mellitus and optic atrophy. Other symptoms include AVP deficiency and hearing loss. Wolfram-like syndrome is caused by an autosomal dominant mutation in the WFS1 gene and characterized by congenital hearing loss, optic atrophy and diabetes mellitus. We describe a case of a boy with Wolfram-like syndrome.

Case report: The boy was born after 38 weeks and 5 days gestation, weighing 2270grams (< -2SD) with multiple dysmorphic features. He had hearing loss and vision impairment. Genetic testing (5GPM) revealed a heterozygous pathological variant c.2425G>A/p.Glu809Lys located in exon 8 of the WFS1 gene. This mutation has been previously reported in 5 different children who developed diabetes mellitus at a very young age; ranging from the age of 3 months to 3 years. At the age of 4 months, after correction of clubfeet, a high glucose of 23mmol/l was measured without ketoacidosis or other symptoms of hyperglycemia. He started on a low dose of insulin detemir with a glucose sensor and after a few days the treatment was changed to subcutaneous insulin via a pump at a dose of 0.4U/kg/day, allowing for his discharge. After 14 days the glucose suddenly increased and remained high continuously. Despite receiving extra insulin glucose levels could not be controlled. He was restless and readmitted again. A few days later he experienced a general convulsion. Despite the administration of anti-epileptic drugs he continued to show epileptic activity on EEG. He was switched to intravenous insulin and the dose had to be increased to about 2U/kg/day to control his glucose levels. Unfortunately, at the age of 5 months the boy died due to severe epileptic encephalopathy following therapy resistant epileptic activity.

Conclusion: Patients with Wolfram-like syndrome can develop diabetes mellitus before the age of 6 months. Glucose levels should be evaluated regularly.