OMIA 001371-9685 : L-2-hydroxyglutaricacidemia in Felis catus

In other species: dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 236792 (trait)

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 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. "

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."

Control: Christen et al. (2021): "The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months."

Breed: Domestic Longhair.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
L2HGDH L-2-hydroxyglutarate dehydrogenase Felis catus B3 NC_018728.3 (100248136..100205236) 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Domestic Longhair L-2-hydroxyglutaric aciduria L2HGDH missense Felis_catus_9.0 B3 g.100207200T>C c.1301A>G p.(H434R) Coding and protein locations are based on XM_023255678.1 and XP_023111446.1, respectively 2021 34062805

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.
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:, 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