UDP-glucose dehydrogenase variants cause dystroglycanopathy.

UDP-glucose dehydrogenase (UGDH) variants have been associated with hypotonia, developmental delay, and epilepsy. We report the first pathologic evidence of dystroglycanopathy in siblings with UGDH variants. Both presented around 6 months with developmental delay and elevated creatinine kinase. Sibling A developed epilepsy at age 9 years. Muscle biopsy from sibling A showed necrotizing myopathy with reduced matriglycan immunostaining. Western blot revealed α-dystroglycan with abnormally low molecular weight. The siblings shared pathogenic UGDH variants in trans: c.305G>A p.(R102Q) is predicted to disrupt protein structure and function; c.265-6C>G is deleterious to splicing. We propose that UGDH is an additional dystroglycanopathy gene.