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

Abstract

AbstractCase DescriptionA 9‐month‐old intact male domestic shorthair cat was evaluated for increasing frequency of generalized tonic‐clonic seizures.Clinical FindingsThe 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.DiagnosticsMagnetic 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 OutcomeLevetiracetam treatment was initiated at 20 mg/kg PO q8h, but the cat died after a seizure 10 days later.Clinical RelevanceWe report the second pathogenic gene variant in L‐2‐hydroxyglutaric aciduria in cats and describe for the first time multicystic cerebral lesions on MRI.