An uncommon cause of optic atrophy in a young male

A 24-year-old male came to our outpatient department with complaints of progressive deterioration of vision over the last few years. He developed insulin-dependent diabetes mellitus at 4 years of age and was started on insulin. He was diagnosed with progressive hearing loss around 12 years of age. He was the only child of a non-consanguineous marriage. His visual acuity was counting fingers at 1 m in both eyes (OU). Anterior segment examination and intraocular pressures were normal OU. Fundus examination revealed pallor of both optic discs with no evidence of diabetic retinopathy [Fig. 1a and b].Figure 1: (a and b) Fundus photograph of right and left eye showing disc pallor suggestive of optic atrophy in both eyes with normal background retina. Magnetic resonance imaging of the brain shows the absence of a pituitary bright spot (white arrow) in image (c) and a thin atrophic optic nerve (white arrowheads) in image (d)What Is Your Next Step? A) Cardiac evaluation, including carotid Doppler, to rule out ocular ischemic syndrome, B) Fundus fluorescein angiography, C) Urine osmolality, D) Panretinal photocoagulation. Findings Based on urine osmolality, which was more than 1000 mm/L, a diagnosis of diabetes insipidus was made. Magnetic resonance imaging of the brain was done, which revealed thin optic nerves, optic tracts, and chiasm. The posterior pituitary bright spot was absent, which was suggestive of Wolfram syndrome [Fig. 1c and d]. Audiometry revealed features of bilateral high-frequency sensorineural hearing loss. An endocrinologist's opinion was obtained. Neurologic examination was normal. The patient was advised genetic testing for the WS1 gene but was not willing for the same. He was advised of low-vision aids and routine follow-up with the endocrinologist. Diagnosis Wolfram Syndrome Correct Answer C) Urine osmolality Discussion Wolfram syndrome is a prototype of endoplasmic reticulum disorder characterized by improper folding of secretory and membrane proteins.[1] This genetic disorder has been classified into classical Wolfram syndrome 1 (WS1) and Wolfram syndrome 2 (WS2). WS2 differs from WS1 by the presence of bleeding, upper intestinal ulcer, defective platelet aggregation, and absence of diabetes insipidus and psychiatric disorders.[2] The presence of optic atrophy in the absence of features of diabetic retinopathy in a patient with type-1 diabetes mellitus may point toward Wolfram syndrome. Current research aims at reducing endoplasmic reticulum stress by employing pharmacotherapeutic agents such as sodium valproate and dantrolene.[3] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.