Neuronal Ceroid Lipofuscinosis 10 (CTSD gene, American Bulldog)

Neuronal ceroid lipofuscinosis type 10 (NCL10) is a disease that results in the accumulation of toxic substances inside neurons in the form of autofluorescent granules or lipofuscin in the cerebrum, cerebellum and retina. In this type of lipofuscinosis the affected gene is the one coding for cathepsin D.

Symptoms

NCL10 in American bulldog dogs is characterized by a later onset of symptoms and slower progression compared to other types of lipofuscinosis. The first signs of the disease usually manifest after 2 years of age. These include hypermetria, dysmetria, paraparesis, ataxia and psychomotor degeneration. Unlike other forms of lipofuscinosis, blindness does not occur in NCL10. Dogs affected by NCL10 can have a life expectancy of up to approximately 7 years.

Disease Management

Unfortunately NCL10 has no cure and treatment is usually focused on alleviating the symptoms and improving the quality of life of the affected dog. If you suspect that your dog has any symptoms related to NCL10, you should see your veterinarian for evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by the accumulation of fluorescent lipofuscin granules in the lysosomes of neurons, resulting in early neuronal death and progressive neurodegeneration of the central nervous system. These diseases are caused by mutations in various genes, the age of onset of symptoms and progression vary with the specific form of the disease and the underlying mutation. The variant that causes this type of lipofuscinosis is c.597G>A of the CTSD gene that codes for the enzyme cathepsin D. In affected dogs, cathepsin D activity is reduced to approximately 36% of normal activity. Cathepsin D is a ubiquitously expressed enzyme that appears to have a relevant function in neurons where it is thought to be involved in the degradation of misfolded proteins in the lysosomal degradation pathway.

Most affected breeds

  • American Bulldog

Bibliography

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