CAD mutation-associated developmental and epileptic encephalopathy-50 with dramatic response to uridine therapy: A case report and a review of the literature

Abstract Background : Developmental and epileptic encephalopathy-50 (DEE-50) is a rare clinical condition believed to be caused by a mutation in the CAD gene and is associated with a bleak prognosis. CAD-related diseases have a wide range of clinical manifestations and other symptoms that may be easily overlooked. Like other rare diseases, the clinical manifestations and therapeutic effects of DEE-50 necessitate further investigation. Case Presentation : A 1-year-old male patient presented with developmental delay, seizures, and anaemia at 3 months of age. He further developed refractory status epilepticus (SE), rapid deterioration of cognitive and motor function, and even became comatose at 5 months of age. Whole-exome sequencing of trios (WES-trios) revealed a compound heterozygous variant in the CAD gene, with one locus inherited from the father (c.1252C>T: p.Q418* nonsense mutation) and one from the mother (c.6628G>A: p.G2210S, missense mutation). After uridine treatment, his cognitive faculties dramatically improved and he remained seizure-free. We reviewed 42 reported cases of CAD variants, 90% of which had onset before 3 years of age, with a mean age of onset of approximately 1.6±1.8 years, and the age at diagnosis was 6 years. The mortality rate was approximately 9.5%, with all reported deaths occurring in patients who received no uridine treatment. This clinical entity can be effectively treated with uridine. Conclusions : We present a case of CAD-associated DEE-50, touch upon the details of clinical manifestations and expand the spectrum of CAD mutations. At 5 months of age, he experienced refractory status epilepticus, rapid cognitive and motor function deterioration, and ultimately fell into a comatose state. Early uridine treatment is recommended if a CAD defect is suspected or genetically diagnosed.