Biochemical Features of Primary Cells from a Pediatric Patient with a Gain-of-Function ODC1 Genetic Mutation

The study described a new autosomal dominant genetic disorder in a pediatric patient caused by a heterozygous de novo mutation in the ODC1 gene, leading to global developmental delay, alopecia, overgrowth, and dysmorphic features. Primary dermal fibroblasts from the 3-year-old patient showed significantly higher levels of ODC protein and putrescine compared to controls, with ODC enzyme activity being 12–17 times higher in fibroblasts and 125–137 times higher in red blood cells. Treatment with the ODC inhibitor DFMO reduced ODC activity and putrescine levels to normal without affecting cell morphology or viability, suggesting that DFMO could be a beneficial treatment for patients with similar ODC1 mutations.