A novel missense variant in the L2HGDH gene in a cat with L-2-hydroxyglutaric aciduria and multicystic cerebral lesions

J Vet Intern Med. 2023 Mar;37(2):676-680. doi: 10.1111/jvim.16675. Epub 2023 Mar 7.


Case description: A 9-month-old intact male domestic shorthair cat was evaluated for increasing frequency of generalized tonic-clonic seizures.

Clinical findings: The cat was reported to have had episodes of circling between the seizures. Upon examination, the cat had bilateral inconsistent menace response but otherwise normal physical and neurological examinations.

Diagnostics: Magnetic resonance imaging (MRI) of the brain identified multifocal, small, rounded intra-axial lesions within the subcortical white matter containing fluid with similar characteristics as cerebrospinal fluid. Evaluation of urine organic acids showed increased excretion of 2-hydroxyglutaric acid. An XM_023255678.2:c.397C>T nonsense variant in the L2HGDH gene encoding L-2-hydroxyglutarate dehydrogenase was identified using whole genome sequencing.

Treatment and outcome: Levetiracetam treatment was initiated at 20 mg/kg PO q8h, but the cat died after a seizure 10 days later.

Clinical relevance: We report the second pathogenic gene variant in L-2-hydroxyglutaric aciduria in cats and describe for the first time multicystic cerebral lesions on MRI.

Keywords: Felis catus; animal model; genetics; glutaric aciduria; neurology; precision medicine.

Publication types

  • Case Reports

MeSH terms

  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Diseases, Metabolic, Inborn* / diagnosis
  • Brain Diseases, Metabolic, Inborn* / drug therapy
  • Brain Diseases, Metabolic, Inborn* / genetics
  • Brain Diseases, Metabolic, Inborn* / veterinary
  • Cat Diseases* / diagnosis
  • Cat Diseases* / drug therapy
  • Cat Diseases* / genetics
  • Cats
  • Glutarates
  • Magnetic Resonance Imaging / veterinary
  • Male
  • Mutation, Missense
  • Seizures / diagnosis
  • Seizures / veterinary


  • Glutarates
  • Alcohol Oxidoreductases

Supplementary concepts

  • 2-Hydroxyglutaricaciduria