A Pair of Siblings With Wolfram Syndrome: A Review of the Literature and Treatment Options

Abstract

Wolfram syndrome (WS) is a rare genetic disorder typically characterized by juvenile onset diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, and neurodegeneration. There would be a high index of clinical suspicion for WS when clinical manifestations of type 1 diabetes and optic atrophy present together. Genetic analysis is often required to confirm the diagnosis. We describe a pair of Chinese siblings diagnosed with WS at ages 20 and 24 years, respectively. DNA sequencing of the WFS1 gene which encodes for Wolframin ER Transmembrane Glycoprotein identified a heterozygous nonsense variant NM_006005.3: c.1999C>T p.(Gln667*) and a heterozygous missense variant c.2170C>T p.(Pro724Ser) in exon 8 of the gene for both siblings. There is no curative treatment for WS and management of this debilitating disease is aimed at treating individual clinical manifestations, slowing disease progression, and improving quality of life. Treatment with liraglutide, a glucagon-like-peptide-1 receptor agonist, and tauroursodeoxycholic acid was started for the younger sibling, the proband. There was reduction in insulin requirements and improvement in glycemic control. The other sibling was not offered liraglutide due to her complex treatment regimen for end-organ failure. Genetic testing is a valuable tool to detect WS early to allow precise and prompt diagnosis, thereby facilitating the coordinated care from a multidisciplinary team of clinicians.

Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1

“…Salzano et al reported heart diseases in 14.3% of 14 patients, including VSDs, and secundum atrial septal defects (ASDs) with concomitant valvulopathy [ 9 ]. ASDs were also described in one of a pair of Chinese siblings [ 10 ]. In 16.1% of 31 Lebanese patients, valvular heart disease, particularly pulmonary stenosis, was described [ 11 ].…”

GLP-1 receptor agonists as promising disease-modifying agents in WFS1 spectrum disorder

“…The authors observed a decrease in insulin requirement, stabilization of neuroophthalmological and neurophysiological disease parameters, and no onset of new WFS1-SD-related symptoms at the latest follow-up (18). Accordingly, a very recent case report described the treatment of a WFS1-SD patient with 0.6 mg per day liraglutide in association with the chemical chaperone tauroursodeoxycholic acid (TUDCA) to mitigate ER stress, reduce insulin requirements, and improve glycemic control (82).…”