Evidence map›Paper›PMID 41803992›Full record

ArticleOrphanet journal of rare diseases2026

Characterizing the frequency of clinical events and assessing biomarkers in propionic acidemia: a natural history study.

Bernd C Schwahn, Gerard T Berry, Hilary J Vernon, Hong Li, J Lawrence Merritt Ii, Manuel Schiff, Brigitte Chabrol, Javier De Las Heras, Jerry Vockley, Chung Lee and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Bernd C SchwahnManchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK.
Gerard T BerryDivision of Genetics and Genomics Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Hilary J VernonDepartment of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Hong LiDepartment of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
J Lawrence Merritt IiDivision of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
Manuel SchiffReference Center for Inborn Errors of Metabolism, Necker University Hospital, APHP and University of Paris Cité, Filière G2m, MetabERN, Paris, France.
Brigitte ChabrolReference Center for Inherited Metabolic Disorders, Assistance Publique Hôpitaux de Marseille, Centre Hospitalier Universitaire de La Timone Enfants, Filière G2m, MetabERN, Marseille, France.
Javier De Las HerasHereditary Metabolic Diseases Unit at Hospital Universitario Cruces (CIBER-ER), Bio-Bizkaia Health Research Institute, University of the Basque Country (UPV/EHU), Barakaldo, Spain.
Jerry VockleyDivision Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Chung LeeDepartment of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, CA, USA.
Dwight D KoeberlDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Barbara K BurtonAnn & Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Stephanie GrunewaldGreat Ormond Street Hospital for Children and Institute of Child Health, NIHR Biomedical Research Center, London, UK.
George A DiazIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Can FiciciogluChildren Hospital of Philadelphia, Philadelphia, PA, USA.
Thomas MorganVanderbilt University School of Medicine, Nashville, TN, USA.
Junxiang LuoModerna, Inc., Cambridge, MA, USA.
Husain AttarwalaModerna, Inc., Cambridge, MA, USA.
Min LiangModerna, Inc., Cambridge, MA, USA.
Sue PereraModerna, Inc., Cambridge, MA, USA. sue.perera@modernatx.com.ORCID http://orcid.org/0009-0003-6086-8389
Vanja SikiricaModerna, Inc., Cambridge, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPropionic acidemia (PA) is a rare disease resulting in toxic accumulation of metabolites that cause metabolic decompensation events (MDEs). Natural history characterization of PA is limited partly due to its rarity and complexity. This study examined clinical events in participants with PA and their correlation with biomarkers to better understand the disease.

methodsParticipants diagnosed with PA (early- versus late-onset) were evaluated every 6 months from baseline to month 36. Outcome measures included annualized MDEs and changes in 3-hydroxypropionic acid (3-HP), 2-methylcitrate (2-MC), and propionylcarnitine (C3) concentrations. Blood samples were collected at each visit and during MDEs for plasma biomarker analyses. Relative risk (RR) was calculated based on MDE rates and biomarker levels.

resultsMost participants (n/N = 49/50, 98.0%) reported MDEs. Annualized MDE rates were highest in participants aged 0 to ≤ 1 and > 1 to ≤ 2 versus > 12 to ≤ 18 years (2.6 and 2.4, respectively, vs 0.2) and for early-onset versus late-onset PA (1.2 vs 0.3). A 50% decrease in plasma biomarkers was associated with a statistically significant reduction in RR of MDEs for 3-HP (RR: 0.7, 95% CI: 0.6–0.9; p < 0.01) and a substantial reduction for C3 (RR: 0.6, 95% CI: 0.4–0.9; p = 0.017); no effect was observed for 2-MC.

conclusionsMDE rates were higher in the youngest participants (0 to ≤ 2 years) versus participants aged > 12 years, and with early- versus late-onset PA. Lower concentrations of 3-HP and C3 were associated with a reduced MDE risk. These findings may guide biomarker or clinical endpoints in future treatment trials.

Indexed as

BiomarkersPropionic AcidemiaCarnitineChild, PreschoolCitratesFemaleHumansInfantLactic AcidMalePropionates2-methylcitric acidBiomarkersCarnitineCitrateshydracrylic acidLactic AcidPropionatespropionylcarnitine2-MC3-HPBiomarkersC3Clinical eventsMetabolic decomposition eventsPropionic acidemiaPropionyl-CoA carboxylase deficiency

Identifiers

PMID41803992
PMCPMC13085267

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.