Background: Propionic acidemia (PA) is a rare genetic disorder caused by a deficiency of propionyl-CoA carboxylase potentially resulting in the onset of metabolic decompensation events (MDEs) that can be life-threatening or lead to long-term complications. MDEs are biochemically characterized by the occurrence of hyperammonemia or metabolic acidosis with high anion gap. The current literature describing the frequency of MDEs in PA patient populations is limited and findings are primarily derived from small case series.
Objectives: To describe patient demographic characteristics and estimate the proportion and total rates of MDEs among patients with PA identified within TriNetX, a US-based real-world data (RWD) source of electronic health records.
Methods: This cohort study included patients in the TriNetX structured dataset with ICD-10 code E71.121, introduced in 2015 to classify PA patients. Patients were required to have ≥1 medical encounter in the follow-up period, to ensure a period of observability. Follow-up began at first-recorded PA diagnosis between 01/2015 and 04/2022 and ended at recorded death or the end of all available data. MDEs were defined by hyperammonemia or metabolic acidosis during an inpatient or emergency room encounter. Demographics were evaluated at baseline and presented overall and within subgroups (patients with and without MDEs during follow-up). The proportion of patients (n, %) with ≥1 MDE, mean and median MDE counts per patient, and the total MDE rate (number of MDEs divided by person-time) were calculated overall and within age subgroups.
Results: Among 269 PA patients meeting cohort eligibility requirements, 85 (31.6%) had ≥1 MDE during follow-up (mean: 3.2, median: 2.8 years); 49 (33.1%) of adults (≥18) and 36 (29.8%) of pediatric patients had ≥1 MDE. During follow-up, 45 (16.7%) of the cohort had a recorded death: 27 (14.7%) patients without MDEs and 18 (21.2%) patients with ≥1 MDE. Among patients with ≥1 MDE, individuals had a mean of 3.0 events and a median of 1.0, with a range of 1 to 37 events per person. The average MDE rate in the overall PA cohort and among a subset with with ≥1 MDE were 0.58 and 1.85 per person-year, respectively. Among patients with MDEs, 73 (85.9%) were hospitalized during an event. Of the total 252 recorded MDEs, 23.8% of the MDEs were characterized by hyperammonemia only, 61.9% by metabolic acidosis only, and 14.3% by both hyperammonemia and metabolic acidosis.
Conclusions: This real-world study describes the largest single cohort of PA patients reported to date, providing insight into the frequency, rates, and clinical drivers of MDEs.
