Clinical and genetic analysis of five children with ornithine transcarbamylase deficiency: two novel mutations

Background: Cases and studies of neurological symptoms caused by genetic metabolic diseases have been widely reported. Ornithine transcarbamylase deficiency (OTCD) is the most common inherited defect of urea genesis, which due to mutations in the OTC gene located on chromosome Xp21.1. In this study, we analyzed the clinical and genetic characteristics of 5 Chinese children diagnosed with OTCD. Methods: A total of 5 patients (2 males, 3 females) from 5 unrelated families were diagnosed with OTCD by biochemical and molecular analysis between 2015 and 2021. Clinical manifestations, biochemical features and OTC gene sequencing analysis were reviewed retrospectively. Results: All the patients were late-onset and the median onset age was 2.9 years (range 1.8–4 years). Neurological symptoms were the most clinical manifestations including coma, dyssomnia and seizure. The peak plasma ammonia levels ranged from 149 to 1263 mmol/L and alanine transaminase (ALT) levels ranged from 64 to1316 U/L. 2 of them had received CRRT treatment and only one patient was admitted liver transplantation. By Dec 2021, 3 patients had survived and 2 were deceased. 4 of them were detected blood amino acids or urinary organic acids. All of them were completed whole-exome sequencing (WES) and two novel mutations were revealed (c.617dupT and c.664-1G>C). Conclusion: OTCD diagnosis was confirmed in the 5 Chinese children by biochemical findings and genetic analysis, together with 2 novel mutations in the OTC gene. These data will contribute to a better understanding of the clinical course and molecular genetic characteristics of Chinese patients with OTCD.