Clinical features and disease progression of L‐2‐hydroxyglutaric aciduria in 27 Staffordshire bull terriers

Abstract

To describe the development of clinical signs (CS) and outcome of L-2-hydroxyglutaric aciduria (L-2-HGA), owners of 119 Staffordshire bull terriers positive for the known L-2-hydroxyglutarate dehydrogenase autosomal-recessive mutations were requested to complete a questionnaire regarding their pet's CS. Questionnaires were returned for 27 dogs, all with neurological abnormalities-not all questions were answered in all cases. The mean age of CS onset was 12 months (range 2.5-60). Gait dysfunction was reported in 26/26 dogs, with stiffness of all four limbs the most common (24/26) and earliest recognised abnormality. Kyphosis (19/26), body and/or head tremors (19/26) and hypermetria (15/26) were frequent. Behavioural changes were present in 24/27 dogs; most commonly staring into space (21/24), signs of dementia (17/24) and loss of training (15/24). Eighteen dogs demonstrated paroxysmal seizure-like/dyskinetic episodes. Nineteen (70 per cent) dogs were alive at a mean survival time of 76.6 months (12-170) after onset of CS. L-2-HGA was the cause of euthanasia in six dogs. Euthanasia occurred at a mean survival time of 44 months (8.5-93) after onset of CS, with 2/8 dogs euthanased within 12 months. L-2-HGA is considered a progressive neurological disease; however, CS can be successfully managed with affected dogs potentially living a normal lifespan.

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

“…14 The age of the cat (14 months) fits with the pattern seen in the Staffordshire Bull Terrier, with a mean age of onset of clinical signs reported at 12 months of age. 3 Interestingly, the clinical signs manifesting in this case were generalised tonic–clonic seizures; however, the cerebral cortex appears to be unaffected on MRI. Seizures or seizure-like episodes are reported in both dogs 2,3 and people, 4 although there is some variation in these episodes, with dyskinesias appearing to be more common in dogs.…”

“…3 Interestingly, the clinical signs manifesting in this case were generalised tonic–clonic seizures; however, the cerebral cortex appears to be unaffected on MRI. Seizures or seizure-like episodes are reported in both dogs 2,3 and people, 4 although there is some variation in these episodes, with dyskinesias appearing to be more common in dogs. No cellular inclusion or lymphocyte changes were seen on blood smear examination.…”

“…This is the first report, to our knowledge, that describes 2-HGA in a cat. Most cases identified in the veterinary literature are the L-2-HGA chiral form of the disease; 2,3,5,6 however, the D-2-HGA form has been reported in an Irish Setter cross Labrador. 14 The age of the cat (14 months) fits with the pattern seen in the Staffordshire Bull Terrier, with a mean age of onset of clinical signs reported at 12 months of age.…”

“…Although, to our knowledge, there is no reported presentation in cats, the condition is well described in dogs with gait dysfunction, body and/or head tremors and seizure-like/dyskinetic episodes reported in Staffordshire Bull Terriers. 3 There are two chiral forms: L-2-HGA and D-2-HGA, with a third, mixed form D-, L-2-HGA reported in human medicine. 4 L-2-HGA has been described in Staffordshire Bull Terriers, 2,3 a West Highland White Terrier 5 and Yorkshire Terriers.…”

“…2-Hydroxyglutaric acidurias (2-HGA) are a group of inherited neurometabolic disorders, recognised in human and canine populations, [1][2][3] occurring as a result of an inborn error of metabolism. Although, to our knowledge, there is no reported presentation in cats, the condition is well described in dogs with gait dysfunction, body and/or head tremors and seizure-like/dyskinetic episodes reported in Staffordshire Bull Terriers.…”