Cohen syndrome with novel VPS13B variants presenting as early-onset diabetes: a case report

Cohen syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the VPS13B gene, classically presenting with developmental delay, distinctive craniofacial features, neutropenia, truncal obesity, and progressive retinal dystrophy. Metabolic abnormalities, including insulin resistance and diabetes mellitus, have been increasingly recognized, but early-onset diabetes with diabetic ketoacidosis remains uncommon. We report a 28-year-old Chinese woman with early-onset insulin-resistant diabetes complicated by recurrent diabetic ketoacidosis and nephropathy. She presented with intellectual disability, characteristic facial dysmorphism, truncal obesity with slender limbs, neutropenia, and visual impairment. Diabetes was diagnosed at 24 years of age, with negative islet autoantibodies and preserved C-peptide levels. Whole-exome sequencing identified two novel compound heterozygous VPS13B variants, including a synonymous variant with predicted splice-disrupting effects and a nonsense variant, confirming the diagnosis of Cohen syndrome. This case expands the mutational and metabolic spectrum of Cohen syndrome and highlights the importance of considering syndromic causes and genetic testing in patients with atypical early-onset diabetes.