We recently identified a new form of autosomal recessive canine NCL in a juvenile Dachshund and determined that this disease resulted from a mutation in TPP1, the canine ortholog of human CLN2. Utilizing this DNA test, we genotyped a litter of 4 dogs from carrier parents. Genotyping indicated that one puppy was homozygous for the mutant allele, two were heterozygous and one was normal homozygous. The litter was followed with physical and neurologic examinations until 10.5 months of age. Funduscopy and electroretinography (ERG) were performed at 3, 7, 8, and 10 months. Brain magnetic resonance imaging was obtained on the affected dog at 10.5 months of age.
Physical examination remained normal for all 4 dogs. Neurologic examination in the affected dog revealed an abrupt onset of dull mentation and cerebellar ataxia beginning at 6.5 months. Intention tremors developed by 8 months. Menace response was absent after 7 months. Pupillary light reflex was incomplete at 7 months and absent by 8.5 months. The dog was blind by 8 months. Ocular motor abnormalities included positional downbeat nystagmus by 9 months. Whole body, myoclonic jerks developed by 10 months. Scotopic ERG a- and mainly b-wave responses were reduced at 7 months. Starting at 8 months of age, the funduscopic changes included patches of color changes and generalized vascular attenuation. By 10 months, the scotopic ERGs were non-recordable with only low amplitude photopic responses. MRI revealed diffuse cerebral and cerebellar atrophy. Histopathology on the affected dog at 10.5 months revealed autofluorescent storage material in the retina, cerebellum and cerebral cortex.
Genotyping enabled us to follow the course of this disease from prior to the onset of any clinical signs. The onset of signs was surprisingly abrupt for a progressive neurodegenerative disease suggesting a threshold effect. Cerebellar and visual deficits predominated early in the disease with progressive loss of retinal function both clinically and on ERG. Declining mental status and myoclonus necessitated euthanasia at 10.5 months. Dachshunds with similar signs should be tested for the TPP1 mutation. Since other forms of NCLs occur in a wide variety of breeds, NCL should be considered as a diagnosis for dogs with signs of progressive visual loss, ataxia, mentation changes, and seizures. DNA tests are available for several breeds but otherwise diagnosis can only be made at post-mortem. Cortical atrophy may be apparent on brain imaging, but this is a relatively non-specific finding.