Evidence map›Paper›PMID 41022783›Full record

ArticleNPJ genomic medicine2025

Biallelic variants in BBOX1 cause L-Carnitine deficiency and elevated γ-butyrobetaine.

Xiao Li, Mehdi Yeganeh, Graham Sinclair, Jill Mwenifumbo, Karen J Jacob, Laura Arbour, Anna Lehman, Bojana Rakic, Frédéric M Vaz, Gabriella Horvath and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2025. 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. Article
  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

12 authors.

Xiao Li *Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Mehdi Yeganeh *Department of Pediatrics, University of British Columbia, Division of Biochemical Genetics, BC Children's Hospital, Vancouver, BC, Canada.
Graham SinclairDepartment of Pathology and Laboratory Medicine, University of British Columbia, Biochemical Genetics Laboratory Children's & Women's Hospital, Vancouver, BC, Canada.
Jill MwenifumboDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Karen J JacobDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Laura ArbourDepartment of Medical Genetics, and the Island Medical Program, University of British Columbia, Victoria, BC, Canada.
Anna LehmanDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Bojana RakicDepartment of Pathology and Laboratory Medicine, University of British Columbia, Biochemical Genetics Laboratory Children's & Women's Hospital, Vancouver, BC, Canada.
Frédéric M VazAmsterdam UMC location University of Amsterdam, Department of Laboratory Medicine and Pediatrics, Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, Amsterdam, The Netherlands.
Gabriella HorvathDepartment of Pediatrics, University of British Columbia, Division of Biochemical Genetics, BC Children's Hospital, Vancouver, BC, Canada.
Maja Tarailo-GraovacDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. maja.tarailograovac@ucalgary.ca.
Sylvia Stockler-IpsirogluDepartment of Pediatrics, University of British Columbia, Division of Biochemical Genetics, BC Children's Hospital, Vancouver, BC, Canada. sstockler@cw.bc.ca.

Funding

Genome Canada and Genome BC 275SIL
6 · The paper itself

Abstract

Gamma-butyrobetaine hydroxylase (BBOX1) catalyses the last step of carnitine biosynthesis, converting γ-butyrobetaine (γ-BB) into L-carnitine. Here we show, for the first time, that biallelic variants in BBOX1 are associated with decreased levels of L-carnitine and increased plasma levels of γ-BB in three patients from two unrelated families presenting with myopathic, neurodevelopmental, and late-onset psychiatric manifestations. Using a knockout C. elegans model of BBOX1 homolog, gbh-1, and strains harboring patient-derived variants (gbh-1(D72G) for p.Asp59Gly, gbh-1(G283R) for p.Gly263Arg, and gbh-1(G247Vfs6) for p.Gly227Valfs*6), we show very low L-carnitine levels and significantly elevated γ-BB in c.675delA and c.787G>A mutants, and moderately elevated γ-BB in c.176A>G. Furthermore, we observed a lethal embryonic phenotype for the gbh-1 loss-of-function strains, which was rescued upon L-carnitine supplementation. Our study provides novel insights into the clinical and biochemical consequences of BBOX1-related L-carnitine biosynthesis deficiency and establishes C. elegans as a model to study the effects of BBOX1 deficiency.

Identifiers

PMID41022783
PMCPMC12480863

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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.