Clinical characteristics, treatments and outcomes of patients with ornithine transcarbamylase deficiency (OTCD): a retrospective cohort study using a US electronic health record database

Background Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked inherited disorder characterized by deficiency of the hepatic mitochondrial enzyme ornithine transcarbamylase, leading to elevated ammonia and glutamine blood levels and associated metabolic and neurological complications. Management with ammonia-scavenging medications aims to mitigate hyperammonemia events (HAEs); however, real-world research on OTCD management remains limited owing to the disease’s rarity. We used data from the Truveta Electronic Health Record (EHR) database (01/01/2016–02/29/2024) and natural language processing (NLP)-derived data from physician notes to describe characteristics, treatments, and outcomes of patients with OTCD in the US. Results A total of 214 patients were included in the analysis. The median age was 36.5 years (79.0% aged ≥ 18); 65.9% of patients were female at birth, and 57.5% identified themselves as White. The median follow-up was 28.7 months. Ammonia-scavenging treatments were used by 21.0% of patients, with higher use among pediatrics (28.9%) compared with adults (18.9%). Glycerol phenylbutyrate was the most frequently used ammonia-scavenging treatment, administered to 17.8% of patients. Commonly observed signs and symptoms included personality/emotional/behavior changes (38.8%), shallow breathing (29.4%), nausea/vomiting (27.1%), lethargy (25.7%), and headache (25.2%). Among the 68 patients (31.8% of the overall cohort) with available ammonia levels, 43 (63.2%) experienced ≥ 1 HAE, with a rate of 0.53 events per person-year (PPY). Event rates were numerically higher among pediatrics compared with adults (0.60 vs. 0.50 PPY). Conclusions These findings underscore a substantial clinical burden in OTCD and reveal limitations of current treatments, underscoring the need for therapies that more effectively prevent HAEs and reduce symptom burden.