A Pathogenic L2HGDH Variant Impairs Mitochondrial Targeting and Enzyme Function in L-2-Hydroxyglutaric Aciduria: Clinical and Functional Evidence from Two Affected Siblings.

Qiang Guo, Thilo Löhr, Patrick Giavalisco, Vera Riehmer, Hans Zempel

Abstract readCase Reports

In one paragraph

Article in Genes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing 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.

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

L-2-Hydroxyglutaric Aciduria Due to the Homozygous Variant c.905C>T in L2HGDH Without Cognitive Deficits or Gait Disturbance: A Case Report.Cureus · 2026
Article

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5 · Who and what money

Authors and funding

5 authors.

Qiang GuoDepartment of Clinical Laboratory, Anhui Children's Hospital, Hefei 230032, China.

Thilo LöhrInstitute of Human Genetics, Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Patrick GiavaliscoMetabolomics Core Facility, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.

Vera RiehmerInstitute of Human Genetics, Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.ORCID 0000-0002-2276-9983

Hans ZempelInstitute of Human Genetics, Faculty of Medicine, University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.ORCID 0000-0002-7510-3077

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundL-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by biallelic loss-of-function variants in the L-2-hydroxyglutarate dehydrogenase (

methodsHA-tagged wild-type and p.(Pro302Leu) mutant

resultsWestern blotting showed that wild-type

conclusionsThese findings indicate that the p.(Pro302Leu) variant leads to aggregation of mislocalized protein, thereby impairing L2HGDH function rather than decreasing enzymatic function. This study provides clinical and molecular evidence supporting the pathogenicity of this previously reported mutation and highlights the importance of mitochondrial import for enzyme functionality in L2HGA.

Indexed as

Alcohol OxidoreductasesBrain Diseases, Metabolic, InbornMitochondriaFemaleGlutaratesHEK293 CellsHumansMaleMutationSiblingsAlcohol Oxidoreductasesalpha-hydroxyglutarateGlutaratesL2HGDH protein, humanL-2-hydroxyglutarate dehydrogenase 3L-2-hydroxyglutaric aciduria 2metabolic disorder disease

Identifiers

PMID40870031

DOI10.3390/genes16080982

PMCPMC12385959

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