Diabetes Mellitus and Optic Atrophy: Not Just a Coincidence

Wolfram Syndrome (WS1) is a rare autosomal recessive genetic disorder characterized by diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss and neurodegeneration. WS1 may be caused by variants in the WFS1 gene that encodes a protein called wolframin. A 10-year-old boy presented to the emergency department for dysuria, polyuria and polydipsia with four days duration. Recent changes in appetite or weight were denied. He had a history of syncope episodes and progressive vision loss since the age of 7 and was recently diagnosed with bilateral optic nerve atrophy. His physical exam was normal and he had a Tanner stage I. Capillary blood glucose measurement was 388 mg/dL and urine test strip presented glycosuria without ketonuria. His blood pH was 7.38, potassium level was 3.7 mEq/L and bicarbonate level was 27.2 mmol/L. He had a normal lipid profile and thyroid function, negative anti-thyroid antibodies, negative screening for celiac disease and negative anti-islet cell and anti-glutamic acid decarboxylase antibodies. Considering the combination of optic nerve atrophy and diabetes mellitus, a genetic study for Wolfram Syndrome was performed and revealed 3 variants: 2 of uncertain clinical significance and one probably pathogenic variant. He had a normal tympanogram and audiogram and abdominal ultrasonography did not reveal any abnormalities. A multiple dose insulin injection therapy was started and he was referred to diabetes and genetics consultation. WS1 has poor prognosis and currently there is no effective therapy for this syndrome. Regular audiologic evaluation will be essential to early identify hearing loss. Therefore, a timely recognition and diagnosis is essential in order to minimize the complications and reduce morbidity and mortality.