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: