Endocrine Abstracts

Wolfram Syndrome Type I Spectrum Disorder (WFS1-SD) is a rare autosomal recessive disease caused by mutations of the WFS1 gene located on chromosome 4 p16.1. The disorder comprises early (<16 years) optic atrophy, diabetes mellitus and hearing loss. Additional manifestations are neurological, renal, bladder and psychiatric.

Case report: An 18-year-old male was referred with possible monogenic diabetes. Optic atrophy had been diagnosed at 10 years of age (decreased visual acuity) and type 1 diabetes at 16 years of age (osmotic symptoms and HbA1c 134 mmol/mol). He had never experienced diabetic ketoacidosis and was treated with insulin. A mitochondrial MT-ND 5 mutation of uncertain significance (ClinVan) had been recorded and invoked as the aetiology of the optic atrophy. Examination confirmed BMI 25, visual acuities 6/24-1 right and 6/24+1 left, optic atrophy, no diabetic retinopathy, normal visual fields, dysdiadochokinesia of tongue, arms/hands, bilateral reduction of triceps/supinator reflexes, absent knee/ankle reflexes and flexor plantar responses. Anti-GAD, Islet antigen 2 and ZnT-8 antibodies were negative. A diagnosis of WFS1-SD was considered and confirmed by the finding of two likely pathogenic WFS1 gene mutations. Both were previously reported but not in this combination. His parents were confirmed as carriers and brother normal.

Endocrine investigations: normal basal pituitary function except for slightly low cortisol level but short tetracosactide and insulin tolerance tests confirmed normal cortisol and growth hormone responses. Water deprivation test normal.

Other investigations: audiometry, ECG, echocardiography, MRI heart, MRI pituitary/brain all normal. Exercise ECG stopped due to fatigue at 82% of age-related predicted heart rate. Discussion This case demonstrates the need to consider WFS1-SD in patients with the combination of optic atrophy and diabetes mellitus of juvenile onset. The finding of a mitochondrial gene mutation delayed the diagnosis of WFS1-SD. The variation in phenotype is demonstrated by this case.