Long-term outcome of urea cycle disorders: Report from a nationwide study in Japan

摘要

Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20 years of age of male and female patients with late-onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (P = 360 mu mol/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion, although current therapy for UCDs has advanced and helped saving lives, patients with blood ammonia levels >= 360 mu mol/L at onset often have impaired neurodevelopmental outcomes. Novel neuroprotective measures should therefore be developed to achieve better neurodevelopmental outcomes in these patients.