The Genetic Disorder Neuronal Ceroid Lipofuscinosis (NCL)

Over the last couple of years I've written 3 articles for the American Bulldog Review regarding the genetic disorder Neuronal Ceroid Lipofuscinosis (NCL). I'll try to condense the information that was in those articles. If you would care to read those articles in their entirety, they're reprinted at the bottom of this page.

Basically, NCL is a disease that results in impulses from the brain not getting through to the muscles. The further from the brain that the impulses have to travel, the weaker the impulses are when they reach the muscles. In reality, the muscles are fine, they just aren't getting the message from the brain to do whatever it is they're supposed to do. Often times, in its early stage, this disease will be misdiagnosed as hip dysplasia. The muscles of the rear end, (which are farthest from the brain), are the first to appear affected. The effect is one of unsteadiness of movement, even clumsiness. The dog will have difficulty standing on polished surfaces (such as tile or hardwood floors), and often will hesitate to travel down a set of stairs or steep embankment. Going up doesn't seem to pose as big a problem.
The disease is usually first noticeable at about 1 ½ to 2 years of age. Until that time the dog will seem completely normal. The disease then slowly progresses, sometimes briefly getting a little better for a few weeks, but then getting worse again. The progression of the disease can be a bit like taking 1 step forward (getting a little better), then 2 steps back (then getting considerably worse). By about 4 to 7 years of age, the dog can barely stand, and continually falls into it is own feces or urine. While there doesn't appear to be any pain associated with the disease, most dogs tend to show some frustration in having so much difficulty standing and then moving. I believe that eventually the impulses that tell the heart to beat, or the lungs to expand and contract doesn't get there, and the dog dies. Most often, the dog is euthanized well before that time. The longest lived dogs with this disease that I am aware of lived to be just over 7 years of age, at which time they were both euthanized.
There is no cure for NCL in dogs or in humans. The most important thing I've found is not to stress the affected dog physically or mentally. This means that vaccinations should probably be discontinued once the dog is showing signs of the disease, obviously not mating the dog or bitch, and no extreme exercise or hard training. While I believe that a natural diet with supplements helps a little, I have no data to back up my belief.
For a dog to be affected by NCL, both it's sire and dam must be carriers of the NCL gene. In a litter of pups where both parents are carriers of the NCL gene, but not affected by the disease, about 25% of the pups will get the disease and have the gene, 50% will have the gene (and therefore be capable of passing it on to future generations), but not be affected by the disease, and 25% will be completely clear of the gene and the disease. To the best of my knowledge, all dogs affected with NCL have come down from Hine's Country Boy mated to Hine's Snowbird (aka Dorsey's Flash). Probably the most influential dogs to watch for (descended from Country Boy/Snowbird) are Boyd's Moleque and her son High Jumping Mikey, and Souza's Koa and his son Matias. These are/were exceptional dogs that have produced numerous offspring, but unfortunately are/were carriers of the NCL gene. Therefore, at least 50% of all their pups will also be carriers of the defective gene.
Here in Australia, a dog known as Cyclone Suzie is almost certainly a carrier of NCL. She is a daughter of Boyd's Moleque bred to Souza's Koa. She has produced several litters here, and has passed the NCL gene on. Therefore, if you're thinking of buying a pup with Cyclone Suzie in its pedigree (even a few generations back), you should make sure that it has been tested for NCL. At present, the only way to test for the disease is to send a blood or tissue sample to the University of Missouri in the U.S. for DNA testing. They charge $40.00 US, and will test to find out whether your dog is "Clear", a "Carrier", or will be "Affected" by the disease. There is no way to tell whether a dog is "clear" or a "carrier" of the gene without DNA testing. If a pup has "Cyclone Suzie" in its pedigree, and the breeder has not had the pup tested, then despite what he says, he cannot know if that pup is a carrier of NCL. It is my belief that it is the breeder's responsibility to test for this disease if his stock comes from the affected lines. Unfortunately, not many do. (Or for that matter, even want to know about it.)

BULLDOGGERS, WE HAVE A PROBLEM (NCL article #1, summer 2003)

I'm Ed NeSmith with Outback Kennels. Many of you know my wife Victoria and I from the Las Vegas shows.
Unfortunately there seems to be another genetic problem cropping up in American Bulldogs. It's an (up to now)
extremely rare nerve disorder called Ceroid Lipofuscinosis. It's called a storage disease, in that the dogs are
missing an enzyme that would ordinarily "eat" the waste material in nerve cells, allowing the cells to become
"clogged", which makes it difficult for the nerve impulses to travel from the brain to the muscles.
While carriers of the disease show no symptoms, affected dogs develop an unsteady movement, particularly
in the rear end. To the uninformed, including many vets, it may appear that the dog is dysplastic, or has spinal
problems. The dogs start showing symptoms at around 15 to 18 months of age, and continue to degenerate
until, I would expect, they will be unable to rise. The oldest afflicted dogs I've seen are now over 6 years
old, and one of the 2 dogs can barely stand. We owned an afflicted dog that we euthanized at 4 1/2 years..
At that time we had tissue samples sent to several universities, and it was the University of Missouri
that was able to make the diagnosis. Diagnosis can only be made via autopsy.
While I have a good idea of where this disease comes from and its mode of inheritance, I'm not 100% sure, and don't want to make statements that may later turn out to be false. I will say that my dog Diesel is most likely
a carrier, and that I believe that dogs down from Hine's Country Boy or Hine's Snowbird may be at risk.
Unfortunately I've been informed that Diesel's pedigree is a phony, and that Country Boy and Snowbird are
his real grandparents on the dam's side. I do not know this to be true, but have reason to suspect that it is.
It seems that the gene responsible to the disease is a basic autosomal recessive gene, but unfortunately there
are no tests to determine which dogs have the defective gene. The disease also occurs in Border Collies, although the symptoms manifest themselves differently. In Border Collies the symptoms are dementia and blindness, with dogs normally euthanized before 3 years of age. The disease also occurs in humans, with children rarely living past 7 years of age. Again this is a genetic problem and not a contagious disease. The common name is Batten's Disease.
If anyone out there has a dog with symptoms that seem to fit this disease, I would appreciate a call. I'm
gathering as much info as possible, and will share this in an upcoming issue of the ABR. However, I will keep
all inquiries concerning specific dogs confidential, unless given specific authority to divulge it. Hopefully,
with the help of the bulldog community, we'll be able to positively identify the mode of inheritance, and the
specific lines that definitely should not be line bred or inbred. Also, if I can be of any help in dispensing information to anyone with a dog that displays the above-mentioned symptoms, don't hesitate to call or e-mail me. There are a couple of tests that owners can perform on their dogs that will give a better indication of whether or not you have an afflicted dog, and what to expect from the disease. My e-mail address is outbackkau@bigpond.com. If we're honest and open about this disease, we should be able to eradicate it!!!

DNA test now available for Ceroid Lipofuscinosis (NCL article #2, winter 2005)

Hi fellow bulldoggers. Back in the "Summer 2003" issue of the ABR I wrote about a genetic problem that had cropped up called Neuronal Ceroid Lipofuscinosis (NCL). At that time there was a bit of speculation about the disease, its genetic mode of inheritance, and in what lines the disorder was likely to pop up. Well, most of the questions have now been answered. Thanks to the University of Missouri, there is now a DNA test (a simple blood test) available to determine whether or not a dog is a carrier of the defective gene. Also, it seems reasonably certain that the known carriers are dogs down from Hines' Country Boy or Hines' Snowbird. One of these dogs was most certainly the first known carrier, however which one is still uncertain. With the help of Matt Boyd, we've discovered that most, if not all, of the known carriers alive now are down from Outback's Diesel or Boyd's/Hines' Moleque. Should you plan a breeding using a dog with one of the aforementioned dogs in his/her ancestry, it would be a good idea to have it tested for the defective gene. There is no way of telling whether or not a dog is a carrier without testing for it. The website for info on testing at the University of Missouri is http://www.caninegeneticdiseases.net/CL_site/mainCL.htm A link to the website is also available on Matt and Suzie Boyd's site http://www.boydsbulldogs.com/ While several of us have seen our beautiful adolescent dogs transformed into crippled adult dogs, there is now no reason why this disease should pop up again as long as we're thorough with our testing and honest about our dog's pedigrees.
I'd like to thank Matt & Suzie Boyd for being so open and honest (as they always are) about the problem since I first brought them information on what was, at that time, only a theory about the disease and it's origins in American Bulldogs. Another person right out front about the problem was Dave Pope. He also never waffled about the disease, but confronted it head on and is totally committed to the betterment of the breed. Finally, I want to thank our whole club's founding members, since they all had to put up with affected dogs, but were always supportive in trying to figure out what the problem was, and worked with Victoria and I and Drs. Levesque & Evans when we had to get samples to be sent to various universities around the country to try to identify the disease. Unfortunately, as a lot of you know, there are a lot of breeders who would have denied that the problem could possibly be in their line, and lied about ever seeing signs of it. Luckily, because of the openness of many of the people involved, there's every reason to expect this disease to be eradicated. If you have any questions about NCL, I'm always happy to dispense what information I have. My e-mail is outbackkau@bigpond.com. I'd also like to thank Casey and Sheila Courtier for using the American Bulldog Review as a forum for whatever's important to the breed. The ABR's the best way I know of keeping up with what's happening, both good and bad, within the breed.
And last, on a lighter note, my wife Victoria, always a glutton for punishment, has decided to start an AB club in Queensland, Australia, where we now spend most of our time. We're (yes, she's roped me into it as well), expecting to have a fun show in August of this year. So, for any of you Aussies out there with American Bulldogs, you can contact Victoria at reinaday@aol.com . Good luck all, and we'll be back in Las Vegas for 1 more show in October!!! Ed NeSmith

This article is dedicated to our beautiful dog Macaraina, whose life was cut short so we could send tissue samples to the various universities in hopes of finding a cure, and whose samples finally led to a diagnosis of the disease.

NCL UPDATE(NCL article #3, spring 2006)

Hi fellow bulldoggers. Last issue I wrote an article about Neuronal Ceroid Lipofuscinosis for the American Bulldog Review. When I wrote the article, I was feeling very positive that we had the disease, for the most part, under control. As it turns out, it appears I was being unduly optimistic. Here are some figures I've received, courtesy of Liz Hansen at the University of Missouri, enumerating the number of dogs so far tested, and the results of those tests. As of 11/22/05, 178 dogs have been tested. 60 dogs "carriers". 104 dogs "clear". 14 dogs "affected". There are 20 more tests pending. This is just the beginning, so it's clear that this is a major issue already. Basically a clear dog bred to a carrier will, on average, produce 50% clear pups and 50% carriers, with no affected pups. 2 carriers bred together will produce 50% carriers, 25% affected and 25% clear pups, on average. With a little thought you can see how just a few breedings, even of carrier to clear, will produce a lot of potential problems for the breed.
The test now looks for a couple of specific genes, and if either of those genes are present, then the dog is either a carrier, or is (or will soon be), affected with the disease. This test no longer looks for "marker" genes to determine a dog's status (somewhere around 70-80% accurate), but now looks for the actual problem gene (100% accurate). I've been criticized lately for making a big deal out of this disorder. I've also been told that this is no different than hip dysplasia, or ichthyosis, or any of the other genetic problems that affect American Bulldogs. One person actually told me that because a certain dog has never thrown an affected pup, there's no reason that he or she should be tested even though he's out of known carriers, and has produced many offspring. While my first instinct was to call people who think this way "money grubbing morons", maybe it's my fault for not making clear the problems with the disease.
First of all, affected dogs seem to show no signs of a problem until they are around 18 months old. This means the owner has quite possibly spent a considerable amount of money, time, and effort feeding, training, and maybe even showing the dog with no clue of the impending problems. This doesn't even begin to take into account the emotional attachment or bond that is a part of any good owner/dog relationship. Just image how you would feel if your favourite dog, one you spend a great deal of time and effort on, suddenly started to look like it has severe hip dysplasia (showing limited control over its back legs.) The dog, while it doesn't appear to be in any pain, has a difficult time walking, and even standing on a slippery surface sees the dog start to do the splits with its hind legs, without even knowing or feeling them move. Many vets, just seeing the dog in the early stages, will guess that it has hip dysplasia. Within the next 1 to 3 years, the dog won't even be able to keep from falling into its own faeces or urine. When it walks it tends to stagger and move haphazardly, especially if it must go down a flight of stairs or over uneven terrain. When it runs, its rear hops and bounces around showing very little control. Normally, by the time the dog is 5 years old, it's been euthanised, as just standing is very difficult, much less trying to spasmodically walk. With hip dysplasia, the average couch potato dog can live a reasonably normal life, even if it has to be on pain killers like rimadyl. Also, except for severely dysplastic dogs, most dogs won't even show signs of a problem until later in life. With ichthyosis, puppies are seen to have skin problems before they're 2 weeks old, and can be euthanised before there is a large emotional or financial investment in them. The pup is never sold, and in fact never leaves the breeders' yard. While I'm not in any way trivializing these very serious genetic problems, they seem much easier for the average pet owner to deal with than NCL.
And finally, as to which dogs to test, let me say that within the next few years it is likely that many people will be demanding that most dogs are certified "clear" of NCL regardless of their pedigrees. I say this because some of the best looking and tempermented dogs in the country will be found to be carriers, and if 2 carriers are bred together, 25% of the pups will become "affected", and 2/3 of the remaining pups will be carriers, capable of passing the defective gene on. While I don't want this to become a witch-hunt, breeders and owners need to know the most influential carriers of the disorder. As I've said before, my dogs (though not particularly influential in the breed) Diesel, GrCh 2 Spots None the Richer, (and now I know) Domani and Gryffyndogge are all carriers. In Matt Boyd's line Moleque and High Jumping Mikie were the most influential dogs that were carriers. Greg Souza recently informed my wife Victoria, along with many people at our show, that Koa and Matias are both carriers. Close to 10 years ago there was a very special breeding that produced Rob Boyd's "Hammer" as well as several other very nice looking dogs. While I do not know if "Hammer" was a carrier, one of his littermates definitely was, and so he and any of his littermates have a 50% chance of being carriers. (I only mention this because my dog 2 Spots is a Grandson of "Romero's Little Moose", a carrier from the above litter). All dogs with any of these dogs in their pedigree need to be tested before breeding! In my opinion, (and I know I'm going to receive a lot of heat for this!!) this does not mean that a carrier cannot be bred. However, it does mean that it should be an exceptional dog, it must not be bred to another carrier, and that if bred to a clear dog, the breeder has a responsibility to test the puppies to determine which are carriers and which are clear before placing or selling them, along with documentation showing the status of each pup. I believe that to breed a carrier is a serious breeder responsibility!!!! Hopefully within 3 or 4 generations there will be no reason to breed to any carriers.
Thanks to the University of Missouri, there is a $40 DNA test (a simple blood test) available to determine whether or not a dog is a carrier of the defective gene, or will be affected by the disease. For puppies, one can send in their dew claws, therefore getting results before they're ready to go to their new homes. There is no way of telling whether or not a dog is a carrier without testing for it. There is virtually no way of telling if a pup will be affected by the disease before he's around 18 months of age without testing for it. The website for info on testing at the University of Missouri is: http://www.caninegeneticdiseases.net/CL_site/mainCL.htm A link to the website is also available on Matt and Suzie Boyd's site http://www.boydsbulldogs.com/ There is also a site dedicated to Border Collies in Australia with NCL. While the symptoms of the disease manifest themselves differently, the mode of inheritance chart at the bottom of the site is the same for our dogs. http://www.mybcsite.com/bccnswwebfiles/clinformation.htm#Genetic%20Inheritance
If you have any questions about NCL, I'm always happy to dispense what information I have. My e-mail is outbackkau@bigpond.com. Let's not rag on each other over dogs that are found to be carriers, but work together and share testing results so we can all make intelligent, informed decisions about our breedings. Knowledge and openness will quickly help us eradicate this disease before it assumes epidemic proportions.
Ed NeSmith