2-Hydroxyglutaric aciduria as a cause for seizure-like episodes in a domestic shorthair cat

Abstract

Case summary A 14-month-old male castrated domestic shorthair cat, which 2 months prior to presentation underwent hindlimb amputation following a road traffic accident, presented for investigation of four suspected generalised tonic–clonic seizures. Neurological examination was unremarkable. Routine blood work (haematology, biochemistry, ammonia, preprandial bile acids) was unremarkable. MRI of the brain identified marked symmetrical T2-weighted hyperintensities of the cerebellum and brainstem, mainly affecting the grey matter. Urine amino acid and mucopolysaccharide levels were unremarkable. Urine organic acids on two separate samples, 35 days apart, identified highly increased excretion of 2-hydroxyglutaric acid, indicative of 2-hydroxyglutaric aciduria. The cat was started on anticonvulsant therapy with phenobarbitone, which, at the point of writing, has improved seizure control, although the cat has not achieved seizure freedom. Relevance and novel information This case report describes the first reported case of a 2-hydroxyglutaric aciduria, an inherited neurometabolic disorder, as a cause for seizure-like episodes in a cat.

L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

“…Epileptic seizure activity has also been reported in a cat previously with 2-HGA; however, the phenotype of the epileptic seizure activity was different. In the previous case [ 5 ], generalized tonic-clonic epileptic seizures were reported, while our case displayed multiple episodes of running frantically around the house, often in circles, for approximately 30–60 s, bumping into obstacles, having altered mentation and autonomic signs, including salivation and often urination. These episodes are similar to those described in some dogs with L-2-HGA [ 6 ].…”

“…In this study, we identified a homozygous L2HGDH :c.1301A>G missense variant in a domestic cat with a history of suspected seizure-like episodes, corresponding MRI-changes and markedly elevated levels of L-2-hydroxyglutaric acid in the obtained urine sample. The combination of the MRI abnormalities (i.e., multifocal, bilaterally symmetrical, T2W hyperintensities, primarily affecting the grey matter in the mesencephalon and metencephalon) appears to be a common feature for L-2-HGA in cats [ 5 ]. Epileptic seizure activity has also been reported in a cat previously with 2-HGA; however, the phenotype of the epileptic seizure activity was different.…”

“…Recently, another cat with similar clinical and biochemical findings was also diagnosed with 2-HGA. In this cat, the causative genetic variant was not investigated [ 5 ]. As this cat also originated in the United Kingdom, it seems remotely possible that they shared the same genetic defect and that the disease allele is present at non-negligible frequency in the local cat population.…”

“…L-2-HGA has since also been described in different dog breeds [ 2 , 3 , 4 ]. Clinical and radiological signs were reported in a cat with 2-HGA, but the causative defect at the molecular level was not reported [ 5 ]. Clinical signs of patients in veterinary medicine typically include gait dysfunction, behavioral changes and seizure-like/dyskinetic episodes [ 6 ].…”

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

“…It is caused by genetic variants affecting the L2HGDH gene encoding L‐2‐hydroxyglutarate dehydrogenase and has an autosomal recessive mode of inheritance. 1 , 2 , 3 , 4 , 5 , 6 , 7 Disease‐causing variants have been reported in humans, dogs (Staffordshire bull terrier, Yorkshire terrier) and 1 cat. 1 , 2 , 3 , 4 , 5 The clinical signs and magnetic resonance imaging (MRI) findings in dogs and cats with L2HGA have been reported previously.…”