Abstract
Aim: To describe the clinical characteristics of patients with Wolfram syndrome (WFS) and diabetes mellitus (DM) in Aotearoa, New Zealand. Review of response to therapy in those treated with glucagon-like peptide-1 receptor agonists (GLP1RA).
Methods: This retrospective cohort study describes 7 patients with WFS1 genetic variants (1 patient with WFS-like syndrome), and DM from 5 New Zealand families (age range 5-33 years, 4 females, 3 males). All are receiving insulin. In 5 patients receiving GLP1RA therapy, we described their pre- and post-treatment biometric parameters, glycaemic control and visual acuity.
Results: Genetic testing identified compound heterozygous variants in the WFS1 gene (inherited from each parent) in five patients. Another two were heterozygous carriers of a single WFS1 missense variant, one of which was associated with uniparental disomy. Among patients receiving GLP1RA therapy, reductions were seen in HbA1c (mean 11.6 mmol/mol) and total daily insulin dose (mean 0.25 units/kg/day).
Conclusions: We report genotypic and phenotypic variability in association with clinical features, including age of onset and severity. GLP1RA therapy was associated with improvements in diabetic control. Longer-term follow-up is required to monitor for sustained benefit and for progression or improvement in other WFS clinical features.