Ceroid lipofuscinosis

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Intracytoplasmic lipofuscin bodies within the cerebrum of a Tibetan Terrier[1]


Neuronal ceroid lipofuscinosis (NCL) is a genetic lysosomal storage disease of dogs characterized by progressive ataxia due to brain and retinal atrophy[2].

This genetic disease results from a ATP13A2 frameshift mutation[3] that results in ceroid- or lipofuscin-like autofluorescent lipopigments forming within cerebellar neurons, retinal cells, and other visceral cells throughout the body. This disease is similar to human Batten disease[4].

Ceroid lipofuscinosis, which has also been reported in cattle, goats, sheep and cats[5], occurs as a result of a nonsense mutation in exon 4 of the canine CLN5 gene[6].

Breeds affected include the American Bulldog, Tibetan Terrier[1], Border Collie[7] and Dachshund.

Clinical symptoms are usually observed at 2 - 3 years of age (5 - 7 years in the Tibetan Terrier[8]) and often begin with blindness in twilight and disorientation. As the disease progress, more obvious symtoms occur, such as behavioral changes (agggression, anxiousness, disinterest in owner), progressive mental and motor deterioration, blindness, ataxia, dementia, partial seizures, uncoordinated muscle movements and loss of coordination. Affected dogs will usually adopt a wide stance and occasional muscle twitching.

A tentative diagnosis can be established by clinical signs in affected breeds, magnetic resonance image, fundoscopy and histological appearance of neurones.

Definitive diagnosis requires DNA testing of buccal swabs[9].

Differential causes of neuropathy include polyneuropathy and gangliosidosis.

There is no known treatment for this disease and most affected dogs are euthanized within 12 months of clinical presentation.

References

  1. 1.0 1.1 Wöhlke A et al (2011) A one base pair deletion in the canine ATP13A2 gene causes exon skipping and late-onset neuronal ceroid lipofuscinosis in the Tibetan terrier. PLoS Genet 7(10):e1002304
  2. Mizukami K et al (2012) Neuronal ceroid lipofuscinosis in border collie dogs in Japan: clinical and molecular epidemiological study (2000-2011). Scientific World Journal 2012:383174
  3. Farias FH et al (2011) A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan terriers. Neurobiol Dis' 42:468–474
  4. Jolly RD & Palmer DN (1995) The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Neuropathology and Applied Neurobiology 21(1):50–60
  5. Jolly RD & Walkley SU (1997) Lysosomal storage diseases of animals: an essay in comparative pathology. Vet Pathol 34:527–548
  6. Melville SA et al (2005) A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border Collie dogs. Genomics 86(3):287–294
  7. Taylor RM & Farrow BR (1988) Ceroid-lipofuscinosis in Border Collie dogs. Acta Neuropathologica 75(6):627–631
  8. Riis RC et al (1992) Tibetan terrier model of canine ceroid lipofuscinosis. Am J Med Genet 42:615–621
  9. Mizukami K et al (2011) Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan. J Vet Diag Invest 23(6):1131–1139
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