OMIA:001371-9685 : L-2-hydroxyglutaricacidemia in Felis catus (domestic cat)

In other species: dog

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 236792 (trait) , 609584 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific name: L-2-hydroxyglutaric aciduria (L-2-HGA)

Molecular basis: Christen et al. (2021) "sequenced the genome of the affected [domestic longhair] cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. " Christen et al. (2023) report a second likely causal variant in a domestic shorthair cat: "An XM_023255678.2:c.397C>T nonsense variant in the L2HGDH gene encoding L-2-hydroxyglutarate dehydrogenase was identified using whole genome sequencing."

Clinical features: Christen et al. (2021): "A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. ... The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. ... The [domestic longhair] cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months." Christen et al. (2023) report a case of a 9-month old male domestic shorthair cat "evaluated for increasing frequency of generalized tonic-clonic seizures. ... 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. ... 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. ... Levetiracetam treatment was initiated [for the domestic shorthair cat] ... , but the cat died after a seizure 10 days later."

Breeds: Domestic Longhair, Domestic Shorthair.
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
L2HGDH L-2-hydroxyglutarate dehydrogenase Felis catus B3 NC_058373.1 (97886153..97842945) L2HGDH Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1535 Domestic Shorthair L-2-hydroxyglutaricacidemia L2HGDH nonsense (stop-gain) Naturally occurring variant F.catus_Fca126_mat1.0 B3 g.97881395G>A c.397C>T p.(Q133*) XM_023255678.2; XP_023111446.2 2023 36880414
1317 Domestic Longhair L-2-hydroxyglutaric aciduria L2HGDH missense Naturally occurring variant Felis_catus_9.0 B3 g.100207200T>C c.1301A>G p.(H434R) XM_023255678.1; XP_023111446.1 2021 34062805

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001371-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Christen, M., Gonzalo-Nadal, V., Kaczmarska, A., Dyrka, M., Guevar, J., Jagannathan, V., Leeb, T., Gutierrez-Quintana, R. :
A novel missense variant in the L2HGDH gene in a cat with L-2-hydroxyglutaric aciduria and multicystic cerebral lesions. J Vet Intern Med 37:676-680, 2023. Pubmed reference: 36880414. DOI: 10.1111/jvim.16675.
2021 Christen, M., Janzen, N., Fraser, A., Sewell, A.C., Jagannathan, V., Guevar, J., Leeb, T., Sanchez-Masian, D. :
L2HGDH missense variant in a cat with L-2-hydroxyglutaric aciduria. Genes (Basel) 12:682, 2021. Pubmed reference: 34062805. DOI: 10.3390/genes12050682.
2019 Nye, G.J., Major, A.C., Liebel, F.X. :
2-Hydroxyglutaric aciduria as a cause for seizure-like episodes in a domestic shorthair cat. JFMS Open Rep 5:2055116919853898, 2019. Pubmed reference: 31245020. DOI: 10.1177/2055116919853898.

Edit History


  • Created by Imke Tammen2 on 10 Jun 2021
  • Changed by Imke Tammen2 on 10 Jun 2021
  • Changed by Imke Tammen2 on 09 Mar 2023
  • Changed by Imke Tammen2 on 23 Mar 2023