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. 2025 Jul 15;20(1):362.
doi: 10.1186/s13023-025-03901-2.

Clinical burden of propionic acidemia in the United States: a claims-based study by age stratum

Geetanjoli Banerjee  1 , Sue Perera  1 , Fan Mu  2 , Erin Cook  2 , Mu Cheng  2 , Adina Zhang  2 , Jessie Jie Lan  2 , Lin Zou  2 , Vanja Sikirica  3   4
Affiliations

Clinical burden of propionic acidemia in the United States: a claims-based study by age stratum

Geetanjoli Banerjee et al. Orphanet J Rare Dis. .

Abstract

Background: Patients with propionic acidemia (PA) may face recurrent metabolic decompensation events (MDEs) and multisystemic complications. This study compared characteristics and clinical outcomes of patients with PA and matched non-PA controls by age stratum.

Methods: Patients with PA from the US IQVIA PharMetrics Plus claims database (10/2015‒6/2022) had their follow-up time partitioned into age strata (0‒2, 3‒6, 7‒12, 13‒17, ≥ 18 years) and were matched 1:1 to randomly selected non-PA controls within each stratum. MDEs were identified as hospitalizations with claims for hyperammonemia and/or metabolic acidosis. Hospitalizations with claims for PA signs and symptoms were evaluated.

Results: Among 191 patients with PA and 230 matched non-PA controls (median follow-up: 2.7 years), patients with PA had more comorbidities (neurologic/nervous system, cytopenias, growth, metabolism, cardiac system; listed in order of frequency) across all age strata. The overall MDE rate for patients with PA was 0.5 per patient-year (PPY) while hospitalizations with various PA signs and symptoms ranged from 0.3 to 0.6 PPY. MDE rates were highest in those aged 3‒6 years (1.4 PPY), lowest in the 13‒17 years stratum (0.1 PPY), and rose again in adults (0.2 PPY). Patients with MDEs (31.4%) had a significantly higher burden of PA-related symptoms and comorbidities than those without; both groups showed even greater differences when compared to controls.

Conclusions: Patients with PA across all age strata, with and without MDEs, experience a substantial burden of disease-related comorbidities, complications, and healthcare visits compared with matched non-PA controls, which highlights the need for improved clinical outcomes in these patients.

Keywords: Administrative claims data; Age stratification; Clinical outcomes; Metabolic decompensation event; Propionic acidemia; Propionyl coenzyme A carboxylase.

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Conflict of interest statement

Declarations. Ethical approval: Institutional Review Board review was not required for this study as it used retrospective deidentified claims data that comply with Health Insurance Portability and Accountability Act regulations. Specifically, studies using retrospective deidentified claims data do not meet the definition of research in human subjects per Title 45 of CFR, Part 46.102(e)(1) and thus, the policy for protection of human research subjects as outlined in Title 45 of CFR, Part 46, including approval or exemption of research from IRB review, does not apply to this study. Consent for publication: Not applicable. Competing interests: GB, SP, and VS are employees of Moderna Therapeutics, Inc. FM, EC, MC, AZ, JL, and LZ are employees of Analysis Group, Inc, a consulting firm that received fees from Moderna Therapeutics, Inc. to conduct this study.

Figures

Fig. 1
Fig. 1
Study design and matching of patients with PA and non-PA control subjects. *The minimum follow-up for a control subject was the follow-up time of the matched patient with PA rounded down to the nearest 6-month increment, up to a maximum of 3 years. For example, for patients with PA with 12, 25, and 35 months of follow-up, matched control subjects were required to have at least 12 (2 × 6), 24 (4 × 6), and 30 (5 × 6) months of follow-up, respectively. Abbreviation: PA, propionic acidemia
Fig. 2
Fig. 2
Sample selection diagram. Abbreviations: ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; PA, propionic acidemia. Note: [1] As patients with PA could contribute to multiple age strata, the sum of age strata exceeds the total number of patients with PA in the study sample
Fig. 3
Fig. 3
Rates of MDEs [1] and hospitalizations with PA signs and symptoms in patients with PA. Abbreviations: CI, confidence interval; MDE, metabolic decompensation event; PA, propionic acidemia; PPY, per person-year. Note: [1] MDE was defined as a diagnosis of metabolic acidosis and/or hyperammonemia occurring in the inpatient setting. MDE with metabolic acidosis and MDE with hyperammonemia were not mutually exclusive
Fig. 4
Fig. 4
Rates of MDEs [1] and hospitalizations with PA signs and symptoms in patients with PA with any MDE. Abbreviations: CI, confidence interval; MDE, metabolic decompensation event; PA, propionic acidemia; PPY, per person-year. Note: [1] MDE was defined as a diagnosis of metabolic acidosis or hyperammonemia occurring in the inpatient setting
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References

    1. Almási T, Guey LT, Lukacs C, Csetneki K, Vokó Z, Zelei T. Systematic literature review and meta-analysis on the epidemiology of propionic acidemia. Orphanet J Rare Dis Feb. 2019;13(1):40. 10.1186/s13023-018-0987-z. - PMC - PubMed
    1. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore MDMIM, Number. 606054. August 8, 2023. Available at: https://www.omim.org/entry/606054#:~:text=Propionic%20acidemia%20is%20an.... Accessed Mar. 22, 2024.
    1. Thomas JA. Organic acidemias. In: Bernstein LE, Rohr F, Helm JR, editors. Nutrition management of inherited metabolic diseases. Cham: Springer; 2022. pp. 187–201.
    1. Tarasenko TN, McGuire PJ. The liver is a metabolic and Immunologic organ: A reconsideration of metabolic decompensation due to infection in inborn errors of metabolism (IEM). Mol Genet Metab Aug. 2017;121(4):283–8. 10.1016/j.ymgme.2017.06.010. - PMC - PubMed
    1. Kaushal M, Athalye-Jape G, Rahman MM, Motta M. Organic acidemias: clinical presentation in neonates. Newborn. 2023;2(4):263–78.

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