Metabolic decompensation events among patients with propionic acidemia across the US: A large electronic medical...

Propionic acidemia (PA) is a rare, inherited, metabolic disorder affecting amino acid metabolism. PA is characterized by periods of catabolism, which can lead to metabolic decompensation events (MDEs), commonly defined by metabolic acidosis and/or hyperammonemia. This retrospective study used TriNetX (1/1/2015-4/24/2022), a large longitudinal, electronic medical record database, to describe the clinical profile and burden of MDEs for patients with PA in the United States (US). Patients with known age were indexed on their first observed PA diagnosis on or after January 2015. Rates of MDEs, MDE-related clinical parameters, and healthcare resource utilization (HCRU) were assessed during the follow-up period (from index to death, end of data, or a 183-day gap in encounters). Among 269 patients with PA (55.0% adults, 51.3% male), 79 patients (29.4%) experienced ≥1 MDE in an inpatient (IP) or emergency room (ER) setting, and 128 patients (47.6%) experienced ≥1 MDE in any setting including the ambulatory setting. The rate of IP/ER MDEs was 0.53 per patient-year (PPY; 95% confidence interval: 0.36, 0.78); visually, rates followed a U-shaped distribution being higher in patients aged 0 to <2 years (0.58 PPY) and adults ≥18 years (0.72 PPY) compared to patients aged 2 to 18 years (0.22-0.34 PPY). Adults' MDEs commonly involved metabolic acidosis (86.7%) while pediatrics' MDEs commonly involved hyperammonemia (43.4-55.6%). Infection was the most common MDE trigger (63.3%); vomiting (45.6%) and seizure activity (41.8%) the most common MDE symptoms. A higher proportion of patients with MDEs died (21.5%) than those without MDEs (14.7%) during the entire study period; patients with MDEs also had a higher proportion of comorbidities and treatment usage than those without MDEs. This study provides the largest assessment of patients with PA across the US and documents the substantial morbidity with a focus on MDE burden, as well as mortality, highlighting clear unmet need.