Wolfram Syndrome: A Genetic Analysis of 2 Brothers

ABSTRACT Objective: Wolfram syndrome (WS) is a rare, autosomal recessive, progressive disease associated with considerable morbidity, even for heterozygous individuals. Our aim was to describe the cases of 2 brothers with WS and emphasize the importance of this syndrome as a differential diagnosis for autoimmune type 1 diabetes. Methods: Two cases of WS were studied by reviewing medical files and performing clinical and imaging examinations and laboratory tests, including WFS1 gene sequencing. Results: The patients were 2 brothers who were both diagnosed with early onset diabetes mellitus (DM) and were found to have bilateral optic nerve atrophy during screening for chronic complications. In investigating other manifestations of the syndrome, both brothers were found to have diabetes insipidus (DI), moderate hypoacusis, and urinary tract alterations. In addition, there were personal and family histories of psychiatric problems. WS was confirmed through genetic sequencing by a homozygous mutation of the WFS1 gene. Conclusion: Early diagnosis of WS is important for improving patient prognosis, anticipating associated complications, and enabling timely genetic counseling for family members. Abbreviations: DI diabetes insipidus DIDMOAD diabetes insipidus, diabetes mellitus, optic atrophy, deafness DM diabetes mellitus MRI magnetic resonance imaging WS Wolfram syndrome