Neuronal Ceroid Lipofuscinosis (NCL)

What is Neuronal Ceroid Lipofuscinosis in dogs?

LysosomeNeuronal Ceroid Lipofuscinosis (NCL) is also known as Amaurotic idiocy or Batten disease, is an inherited lysosomal storage disease of the nervous system that results in degenerative changes of particular regions of the brain such as the cerebellum as well as in the spinal cord. Neuronal Ceroid Lipofuscinosis is a progressive disease with symptoms that get worse over time and particularly as the amount of degeneration of the central nervous system increases. It is inherited as an autosomal recessive trait, so can skip one or more generations before revealing itself in an affected dog.

Genetics of Neuronal Ceroid Lipofuscinosis

As an autosomal recessive disease, an affected dog must have two copies of the mutated CTSD or PPT1 gene responsible for Neuronal Ceroid Lipofuscinosis. Dogs with only one copy of a mutated gene and one normal copy will show no signs of Neuronal Ceroid Lipofuscinosis just like a clear dog with two normal copies of the CTSD or PPT1 gene. The mutation is known as a point mutation, meaning that just one point in the gene is changed in the mutated form for it to have the consequences it does. This mutation reduces the activity of the enzyme Cathepsin D. This enzyme is required to breakdown particular proteins within the cells and the failure to do this results in the build up of these proteins with negative effects on the cells. The cells of the nervous system are very sensitive to this build up and fail to work properly.

What is the severity of Neuronal Ceroid Lipofuscinosis?

Neuronal Ceroid Lipofuscinosis is a highly severe disease that starts to affect dogs at the prime of life and reduces their remaining lifespan to just a few years of progressively worse symptoms.

What are the symptoms of Neuronal Ceroid Lipofuscinosis in dogs?

Clinical signs of Neuronal Ceroid Lipofuscinosis will begin from about 1-3 years of age in affected dogs and are generally consistent with other neurological diseases. Affected dogs will have a lack of muscle coordination, difficulty balancing and have a very abnormal gait. Often, they will have a wide stance, muscle twitching and a change in behaviour. Progression of Neuronal Ceroid Lipofuscinosis is relatively slow but the mental and muscle deterioration will worsen and the dog may display symptoms reminiscent of Dementia including a loss of learned behaviour, aimless wandering and confusion, frequent and unwarranted barking, depression and even unprovoked aggressive behaviour. Most often the affected dog is euthanized before the disease becomes fatal when the dog has difficulty with normal tasks such as walking and standing. This progression usually takes about 1 – 2 years.

Diagnosis of Neuronal Ceroid Lipofuscinosis

Diagnosis of Neuronal Ceroid Lipofuscinosis is best made using a DNA Disease Screening test to look directly for the mutated CTSD or PPT1 gene and make the diagnosis definitive.

Treatment of dogs with Neuronal Ceroid Lipofuscinosis

Treatment options for dogs with Neuronal Ceroid Lipofuscinosis are limited to making the life of the affected dog as comfortable as possible and reducing the hazards to the dog that is affected by dementia. Keeping the dog in familiar surroundings will help to lessen the stress of a Neuronal Ceroid Lipofuscinosis affected dog during periods of confusion.

References

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Awano T, Katz ML, O’Brien DP, Sohar I, Lobel P, Coates JR, Khan S, Johnson GC, Giger U, Johnson GS. A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis. Mol Genet Metab. 2006 Nov; 89(3):254-60

Awano T, Katz ML, O’Brien DP, Taylor JF, Evans J, Khan S, Sohar I, Lobel P, Johnson GS. A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab. 2006 Apr; 87(4):341-8. 

Evans J, Katz ML, Levesque D, Shelton GD, de Lahunta A, O’Brien D. A variant form of neuronal ceroid lipofuscinosis in American bulldogs. J Vet Intern Med. 2005 Jan-Feb; 19(1):44-51

Mizukami K, Chang HS, Yabuki A, Kawamichi T, Kawahara N, Hayashi D, Hossain MA, Rahman MM, Uddin MM, Yamato O. Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan. J Vet Diagn Invest. 2011 Nov; 23(6):1131-9

Sanders DN, Farias FH, Johnson GS, Chiang V, Cook JR, O’Brien DP, Hofmann SL, Lu JY, Katz ML. A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Mol Genet Metab. 2010 Aug; 100(4):349-56. 

Studdert VP, Mitten RW (1991). Clinical Features of Ceroid Lipofuscinosis in Border Collie Dogs. Australian Veterinary Journal 68: 137-140

Taylor RM, Farrow BR. (1992) Ceroid lipofuscinosis in the border collie dog: retinal lesions in an animal model of juvenile Batten disease. Am J Med Genet. 1992 Feb 15;42(4):622-7

 

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