New variants of Wolfram syndrome (WS) in an Ecuadorian population. The “Valdivia Project”. A Cross-Sectional Study.

Objective: This study aims to document the first genetically confirmed cases of WS 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 WS or not (NSW). Results: This Ecuadorian cohort included 38 participants (19 males) aged <35 years with an average diabetes onset at 3 years old. Eight are siblings, and 5 are first cousins. Genetic studies tested positive for WS 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 WS and in 4/11 NSW 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 WS prevalence worldwide and two novel WS1 variants. In addition, there is high consanguinity and frequency of severe, early clinical complications among WS patients. Only 11% were diagnosed with type 1 diabetes. Must be phenotyping patients with early onset diabetes.