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

Abstract

CASE DESCRIPTION: A 9-month-old intact male domestic shorthair cat was evaluated for increasing frequency of generalized tonic-clonic seizures. CLINICAL FINDINGS: 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. DIAGNOSTICS: 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. 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 OUTCOME: Levetiracetam treatment was initiated at 20 mg/kg PO q8h, but the cat died after a seizure 10 days later. CLINICAL RELEVANCE: We report the second pathogenic gene variant in L-2-hydroxyglutaric aciduria in cats and describe for the first time multicystic cerebral lesions on MRI.