OMIA:001371-9685 : L-2-hydroxyglutaricacidemia in Felis catus
In other species: dog
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 236792 (trait) , 609584 (gene)
Links to MONDO diseases:
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.
|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|
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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||Inferred EVA rsID||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|
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.|
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