309 - Retrospective Study of Propionic Acidemia Using Natural Language Processing in Mayo Clinic Electronic Health Record Data

Propionic acidemia (PA) is a rare, autosomal recessive organic acidopathy that classically presents within the first days of life with a metabolic crisis or via newborn screening and is confirmed with laboratory tests.

Objective:

To describe the natural history of patients with PA using structured and unstructured Electronic Health Record data from the Mayo Clinic.

Design/Methods:

This retrospective study used an augmented curation model to enhance analysis of structured data (ICD-9/-10 codes, CPT codes, medication orders); additional data elements were extracted from unstructured clinical text (medical notes, pathology reports). De-identified medical records were also reviewed manually to ensure data accuracy and completeness. Results were reported as aggregate descriptive statistics relative to patients’ index dates. Complications, therapeutic interventions, lab tests, procedures, and hospitalization encounters related to PA were described at and within 6 months of index date, and from medical history.

Results:

Thirteen patients with PA were identified, with visits occurring from 1998-2022. Age at diagnosis ranged from birth to 3 years; age at initial evaluation at the Mayo Clinic ranged from 3 days to 28 years. The mean number of Mayo Clinic visits was 9.5 (median duration of care, 2.2 years). PA-related complications were diagnosed in 85% of patients, including metabolic decompensation events (MDEs; 38%), cardiomyopathy (7%), neurologic abnormalities (38%), and nutritional difficulties (46%). Two affected siblings had mild symptoms and no complications or MDEs. Although disease severity varied in this cohort, all 13 patients were treated with carnitine supplementation. Five patients had a history of MDEs; all 5 presented with developmental delays. Among patients with MDEs, mean frequency of outpatient clinical care visits was 10.4/year and inpatient hospitalizations occurred in 3 patients (mean duration, 15.7 days). The incidence of severe complications was higher among patients with MDEs vs those without MDEs. Of patients with MDEs, 2 had crises while treated at the Mayo Clinic; annualized MDE rates for these 2 patients were 1.8 and 4.4, respectively. In total, 9 MDEs were reported between the 2 patients; symptoms at presentation included hyperammonemia (78%), fever and/or decreased nutritional intake (67%), hyper/hypoglycemia (56%), intercurrent URI and/or lethargy (44%), constipation (33%), altered mental status (33%), and cough (33%).

Conclusion(s):

This study highlights the range and frequency of clinical outcomes experienced by patients with PA and demonstrates the clinical burden of MDEs.