A previously healthy girl was diagnosed with antibody-negative DM at the age of 5 years. New generation sequencing showed a double heterozygous mutation of the WFS1 gene. Comorbidity screening showed initial optic nerve involvement at magnetic resonance imagine (MRI) and optical coherence tomography (OCT) evaluation.
Liraglutide (LG) was identified as the most promising disease-modifying candidate with the safest pediatric profile and was started at age 8 years.
After 6 months treatment with LG 1.2 mg/day:basal and peak Cpeptide (ng/mL) at the mixed meal tolerance test improved from 0.14 (blood glucose 109 mg/dL) and 0.31 (blood glucose 211 mg/dL) to 0.19 (blood glucose 95 mg/dL) and 0.4 (blood glucose 93 mg/dL) respectively. Glucose time in range improved from 66% (time in hypoglycemia 2%) to 78% (time in hypoglycemia < 1%). Daily insulin needs reduced from 0.4U/Kg to 0.3U/Kg. OCT did not show significant progression in retinal nerve fiber layer (right 71-74 micron, left 68-68 micron) and ganglion cell-inner plexiform layer thickness (right 70-68 micron, left 69-69 micron). No significant gastrointestinal symptoms were reported.
GLP-1R agonists are potential drugs in WS because of their role in decreasing ER stress in both -cells and neurons. Only one LG-treated WS patient has been reported in literature. This is, to our knowledge, the first reported pediatric cases of WS treated with LG with apparent improvement in C-peptide and stabilisation of OCT parameters at 6 months and no adverse events. Longer and larger population RCT studies are warranted prior to it becoming used in routine care.