Abstract
OBJECTIVE: This study aims to document the first genetically confirmed cases of WS1 in Ecuador. DESIGN AND METHODS: A Cross-Sectional study was conducted among individuals with early-onset insulin-dependent diabetes, residing in Santa Elena Province, Ecuador. A detailed clinical history and family tree were obtained along with laboratory and imaging diagnostics. A genetic whole exome sequencing was performed to confirm WS1 or not (NWS). RESULTS: This Ecuadorian cohort included 38 participants (19 males) aged < 35 years with an average diabetes onset at 3 years old. Approximately 50% of the patients are related by consanguinity. Genetic studies tested positive for WS1 in 26 (69%) patients, which yields a prevalence of 1/12,000 inhabitants and the presence of two previously undescribed variants located in exon 8. Twenty-three were homozygous. Positive antibody testing was reported in 3/26 WS1 and in 4/11 NWS patients. High prevalence of severe and early neurological complications: optic atrophy, deafness and urinary disorders were documented. No patient had diabetes insipidus. CONCLUSIONS: Findings suggest the highest WS1 prevalence worldwide and two novel WS1 variants. There is high consanguinity and frequency of severe, early clinical complications among WS1 patients. In addition, only 11% were diagnosed with type 1 diabetes, suggesting that younger patients with early-onset, non-autoimmune diabetes should undergo comprehensive genetic testing.