Neuronal Ceroid Lipofuscinosis
A very recent article was published in the Journal of Veterinary Internal Medicine regarding a Cane Corso and a rare genetic disease called Neuronal Ceroid Lipofuscinosis. Not soon after this article’s publication, there was a lot of discussion regarding its implications for some answers to the devastating disease plaguing the Cane Corso- idiopathic epilepsy. It is our goal to clarify this complex disease to the best of our ability, and to rectify some misconceptions, which may have inadvertently been created as a result of the potential implications in this study. First, it is important to explain this disease, which is commonly referred to as NCL.
NCL is often referred to as a Lysomal Storage Disorder. A Lysosome is an organelle of eukaryotic cells (cells with a nucleus), which houses enzymes responsible for digesting, or degrading specific proteins, carbohydrates, fats, and cellular waste products. A Lysosome can contain 50 different enzymes, each of which is designed to digest a specific type of waste product. Once the Lysosome has done what it was designed to do, which is essentially be the stomach of the cell, and the enzymes within the Lysosome (just as stomach acid in the stomach) have broken down the waste products into useful, and more simple compounds, which are then used for new cell building materials outside the Lysosome. When a mutation occurs regarding the Lysosome, the Lysosome ends up missing one of the enzymes responsible to breaking down a specific type of cellular waste. Without that one enzyme, the waste products, for which that one enzyme was responsible, are not degraded, and so begin to build up onto other cells. For reasons outside the purpose of this article, the other cells, on which the undigested waste products collect, tend to be neuronal cells and retinal cells. Other cells will also collect the undigested waste, but they primarily congregate on neuronal and retinal cells.
There are many forms, or mutations, of this disease. In humans, it is classified very differently than in dogs. In dogs, there tends to be trends within a breed regarding specific symptoms, order of symptom onset, age of symptom onset, and the rate of disease progression. Regardless of the breed, the mutation is relatively similar across all breeds, and yet distinctly different. Most recent literature reports 8 different mutations in dogs. As mentioned, there are symptom trends in specific breeds. For example, in American Bulldogs, the first sign of this disease is generally reported as a lack of coordination in the rear while moving. This lack of coordination advances to a wide- based stance. There are no reports of seizures or visual changes in this breed, but the dogs who suffer from this disease will generally progress to the point where they are no longer to get up without assistance. In Chihuahuas, they will typically begin with changes in mentation, specifically becoming aggressive. There are reports of Chihuahuas circling and having visual impairment, but no seizures have been reported. Dalmations have a much more dramatic display of this disease and will typically start showing symtoms as early as 6 months of age by way of visual impairment which likely progresses to complete blindness. There have been reports of behavioral changes towards aggression, teeth grinding and reports of gait changes such as stumbling and tremors. Dalmations are a breed which so typically begin having seizures associated with this disease around 15-20 months. Tibetan Terriers tend to have a later onset of disease than many other studied breeds, where symptoms do not appear until 4-6 years of age. These dogs will show signs of behavioral changes such as aggression towards people and other dogs. They are known to have visual changes, mostly in dim lighting, and gait changes the display as crossing over while walking, stumbling, inability to jump on and off surfaces, and eventually falling over. These are just a few examples of the many breed which have had research done to identify NCL in the breed, isolate symptoms, and confirm by necropsy. The disease is detectable on necropsy because, the waste products that build up on neuronal and retinal cells, will fluoresce under ultraviolet light microscope.
Without further research in the Cane Corso, we are left with one confirmed case by which we gauge symptoms, symptom onset, and rate of disease progression. While a general search of NCL on the internet may list seizures as a possible symptom, this has not yet been proven to be a symptom of NCL in the Cane Corso. Also, one should consider that NCL is now identifiable in the Cane Corso because of the recent research. However, with research published from only one case, it is inaccurate to say that a Cane Corso with seizures has NCL just as it is inaccurate to say and Cane Corso who has rear limb instability has NCL considering the prevalence of hip dysplasia and knee injuries and disease in the Corso.
Submitted by Stephanie Rudderow