OBJECTIVES: This study aims to describe the characteristics, treatments, and outcomes of patients with ornithine transcarbamylase deficiency (OTCD), a rare urea cycle disorder, causing accumulation of nitrogen, in the form of ammonia, leading to hyperammonemic events (HAEs) and long-term neurological/cognitive complications.

METHODS: This retrospective cohort study utilized the Truveta electronic medical record database (cutoff: 29Feb2024) and enrolled patients at their first medical encounter having SNOMED code 80908008 indicating an OTCD diagnosis. Patient characteristics, treatments, and outcomes were assessed using structured data and natural language processing derived-data from physician notes. Outcome event rates, inclusive of recurring events, were reported during follow-up.

RESULTS: Among 221 patients, the median age was 33.5 years (77.8% of patients aged ≥18; range: 0-87.2 years), 66.1% were female, 57.5% were White, and the median follow-up was 31.1 months. During follow-up, 21.3% (n=47) used ammonia scavenger treatments, with glycerol phenylbutyrate (17.2%) being the most common. Common acute symptoms suggestive of hyperammonemia included personality/emotional/behavior changes (39.8%), shallow breathing (30.3%), nausea/vomiting (29.0%), headache (26.7%), and lethargy (25.8%). Among 74 (33.5%) patients with ammonia levels measured during follow-up, ammonia concentrations varied across patients, with maximum values ranging from 15.0 to 636.0 µmol/L (median [IQR]: 64.5 [40.3, 166.5]; mean: 117.1). Among these patients, 63.5% (n=47) reported ≥1 HAE (defined as hospitalization or emergency room visit with ammonia ≥50 µmol/L for patients aged ≥1 year and ≥80 µmol/L for patients aged <1 year, or hyperammonemia confirmed in clinical notes during hospitalization). The HAE event rate was 0.47 (95%CI: 0.39, 0.55) events per person-year (PPY), higher in children than adults (0.50 vs. 0.45 events PPY). Fifteen patients (20.3%) experienced hyperammonemic crises (defined as HAEs with ammonia ≥200 µmol/L) with an event rate of 0.10 (0.07, 0.14) events PPY.

CONCLUSIONS: Real-world evidence demonstrates a high symptomatic burden and HAE/crisis event rates, indicating a significant clinical burden in OTCD patients.