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

Abstract

Abstract 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.

The authors' abstract, as published at the source. Orphanet Journal of Rare Diseases, 2026 · DOI ↗