NCL10 in American Bulldogs

Neuronal Ceroid Lipofuscinosis (NCL) is an inherited neurodegenerative disease characterised by accumulation of autofluorescent lipopigments (ceroid and lipofucsin) within the cells of the nervous system.
In American Bulldogs, NCL10 type caused by transition G>A in the cathepsin D gene (CTSD-gene), resulting in conversion of methionine-199 to an isoleucine (Awano T. et al, 2006).
The clinical signs of NCL10 in American Bulldogs occur first between the ninth month and three years of age and get progressively worse.
Due to accumulation of lipopigments, the transfer of important information from the brain to muscles stops progressively. In early stage of the disease, it is often wrongly diagnosed as dysplasia of hip joint. First, the hind limbs are affected that are furthest from the brain.
In affected dogs, progressive ataxia and hypermetria of hind limbs and forelimbs develop and the typical splayed posture of hind limbs and clumsiness occur that progresses to the forelimbs.
The jump reaction of hind limbs is delayed. The affected dogs show frequent muscle twitching, mainly during sleep. In advanced stages, all four limbs are stiff; the affected dog has trouble standing up, falls down and practically cannot stand on its feet. The affected dogs die or must be euthanized in the third to fifth year of age.

NCL10 is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

Publication:
Awano T. et al.: A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab 87:341-8, 2006
Evans J. et al: A variant form of neuronal ceroid lipofuscinosis in American bulldogs. J Vet Intern Med 19:44-51, 2005