Neuronal Ceroid Lipofuscinosis – NCL 10 American Bulldog Type
NCL 10 American Bulldog Type is an inherited lysosomal storage disorder. It is a form of group of neurodegenarative disorders, the neuronal ceroid lipofuscinoses (NCLs). They are known to affect humans, cats, sheep, goats, monkey, cattle etc. The neuronal ceroid lipofuscinoses (NCLs) are divided into genetically distinct forms, all causing accumulation of lipopigments in the body’s tissue. To date NCLs have been associated with 8 different genetic mutations. Another classification of NCLs includes age of onset, so they are divided into infantile (INCL), late-infantile, juvenile and adult onset forms. NCL 10 American Bulldog Type differs from other forms of NCLs, due to its impact on locomotion and no affect on the vision of the dog.
Lipofuscin is a yellow to brown lipopigment composed of residues of lysosomal digestion. It is considered to be one of the aging pigments localized in the liver, kidney, heart muscle, retina, nerve cells and ganglion cells. Lipofuscin in high levels causes membrane damage, damage to mitochondria and lysosomes. Its balance within the cell is realized via formation and disposal mechanisms. When this balance is disrupted, accumulation of lipofuscin occurs. In humans, this condition is related to several diseases, such as degenerative disease of the eye, the macular degeneration and inherited juvenile form of macular degeneration, the Stargardt disease, as well the Alzheimer’s, Parkinson’s disease etc. Abnormal accumulation of lipofuscin is cause of the neuronal ceroid lipofuscinosis, causing progressive and permanent loss of motor and psychological ability.
Characteristics and Symptoms
Neuronal Ceroid Lipofuscinosis 10 is a young adult form of NCL affecting American bulldog breed. First symptoms develop between 1 and 3 years of age, most commonly before the second year of age. Affected dogs exhibit hypermetria and ataxia with progressive psychomotor detoration present in all four limbs. A wide-based stance of the pelvic limbs is observed, which eventually progresses on all four limbs.
Histopahological examination of the brain reveals light brown hue in the entire external surface of the brain. Accumulated lipofuscin is present cerebral cortex, brainstream, and cerebellum. Axonal swelling is present in the brain and the spinal cord.
Due to severity and progressive nature of NCL1, affected dogs are usually euthanized by their owners due to humane reasons.
A neurodegenerative disorder with same age of onset and similar features of NCL10 has been identified in the American Staffordshire Terrier and the Pit Bull Terrier, two closely related breeds to the American Bulldog. However, the lipofuscin accumulation and neurodegeneration in these two breeds has been found only in cerebellar Purknje cells and in the certian thalamic nuclei.
NCL 10 American Bulldog Type is caused by a mutation in the Cathepsin D (CTSD) gene. Researches have shown that NCL 10 affected American Bulldog Terrier has a dsignificant decrease in enzyme activity, to 36% in comparison to healthy, unaffected dogs.
Neuronal Ceroid Lipofuscinosis American Bulldog Terrier Type (NCL 10) is inherited as an autosomal recessive disorder. Dog carrying one copy of the mutated gene is heterozygous and will not show the NCL10 symptoms. When mating two carriers (heterozygotes) at conception each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Currently there is no cure for NCL10.