Storage Disease and Cerebellar Abiotrophy in Lagotto romagnolo
Hopefully this written story will awaken everybody.
My name is Kiia Montonen, Holst until august 2011, and I´m from Finland. I´m the breeder, with Kennel name Romagna Valley´s, that had the first two pathologically examined male lagottos from my last litter. This is the beginning of the discovery of the new neurological disease in Lagotto romagnolo, The Storage Disease. It is a disease where there is a lack of some enzyme in the cells and material is therefore stuck in the cells and destroys the cells one by one. There is no known cure for this disease. Still we do not know what kind of material is stored in the cells eventhough the pathological examinations has shown that cells in other parts of the body are also affected, for example the prostate.
I am hoping for serious commitment of every breeder of this lovely breed Lagotto romagnolo. It is time to take this matter in to consideration and act on it right now, this is a disorder that really genetically passes on to the next generation. Fortunately, The University of Helsinki in co-operation with The University of Bern have found the gene and there is a test for this disorder. The test will soon appear on the market and every lagotto can be tested for this fatal disease that is recessively inherited from both parents. The test will be performed by Genoscoper laboratories in the near future. A carrier of this disease is not affected at all. The dog needs to inherit the faulty gene from both parents to get affected and to get symptoms that starts to show in the age of 4 months to 4 years of age. The symptoms are very much alike the symptoms in the Cerebellar Abiotrophy disease that my puppy got diagnosed in 2003. At first there was this thought that my two lagotto-boys had Cerebellar Abiotrophy and it was only by the autopsy that The Dog Genetics Research group of The University of Helsinki could for sure know that this was not Cerebellar Abiotrophy. The dame of my litter is also autopsied and she had not any disease at all at the age of 10 years, she got the gene test result “carrier” of this Storage Disease. My other old lagotto-bitch is also autopsied, but I have not got the report yes, but the gene test result was “normal ” considering this Storage Disease.
It is time to get serious and read the stories written by the owners of my two lagotto boys and the story of my Vilma The Cerebellar Abiotrophy lagotto.
This is Remu´s story: “Remu was both a show dog and an agility dog. Remu was a very energetic
young male with a curious brave temper and was very motivated but enthusiastic and did everything he was told to do with the engine running at full speed. You can say he had a good sense of humor and was very playful and played tricks as well to people and fellow dogs. The qualities and the temper was everything I had hoped for. We had great plans for the future. I started to get worried about Remu´s eyes at the age of one year. At that time there was occasionally some odd movement in the eyes, especially if he was tired. Remu had also a very hard time to learn to pee outside, it took a long time for him to learn to do it outside the house. “Accidents” happened at nights. Remu was with me and my other lagotto male at the agility-training field from a very young age. The trainer told me Remu had got a hard temper that is very good for a working dog and gives more opportunities to train. Remu had none what so ever glimpse of sensitivity and was very fearless. In a non-official character test we got the result of a hardheaded dog and both the judge and I were quite surprised of the result. The judge was very surprised of the very short time it took for Remu to recover from the hard parts of the character test. Remu was through the whole test very
self-confident, as well as fearless and brave. This test was done in the fall 2012. It was during the spring 2012 when the movement in Remu´s eyes came more forth and I saw more of the strange movements, nystagmus. The eyes moved very quickly and started to appear more and more often and soon it was on a daily basis. It was during this same period that Remu started to bite people he even knew. At first we considered this as some misbehaving and even as something he had learned. He even bit the judge at his last dog show and this started a period of heavy training and socializing. I was very surprised that the training of several months did not have any effect on the dog but just did the opposite…the situation got worse. We got to the fall 2012 and we started to have more difficulties around strange people and this was at the worst in the dark. Remu constantly glimpsed backwards and listened very carefully to people that walked by or cars that drove by. It was obvious that he was scared. At this time, me and Kiia, really started to wonder what caused this kind of behavior in the dog that used to be so brave and self-confident. But we could not come up with a conclusion. A clear turn to the worse was ahead when Remu started to bite people he was familiar with and without any warning. The next day he had severe problems controlling his body at the agility training course. He could not control his back legs as normally. This was the kick for me and Kiia to turn to the
specialist of neurology at the Helsiki University, Tarja Pääkkönen, DVM, Dipl ECVN. Now the research started and we could start to wait for results of what was wrong with the dog. Kiia was with us during the proceedings that started in October 2012 and the preliminary neurological examinations with support of the MRI-scan they suspected that Remu had The Cerebellar Abiotrophy. The diagnose was not conclusive because of the lack of the autopsy report. They put Remu on painkillers, and this medication got a long for several months, because it seemed to calm him down. Finally we had an explanation for Remu´s change in temper and character, but on the other hand the news was very sad and tough…I had to be the one making the decision about how long I could have the dog and how long I could let the disease get more severe and where to draw the line to what is a life worth living for Remu. But as soon as Remus condition got worse, he had trouble waking, and he walked in circles non-stop, I had no choice but to put him to sleep. Remu was euthanized in January 2013 at The Helsinki University and the group of Dog Genetics Research got his remains and the histopathology exam shoved that Remu had The Storage Disease”
This is Tahvo´s story: “Tahvo was a very tender and kissing dog from the beginning. He wanted always to be where I was. His character and temper was sweet and kind. The first things we spotted that was strange was Tahvo´s clumsiness but we thought it was just puppy-kind of movements and therefore normal. It did not, however, get any better as the time went by and he had very difficult of learning to lift his blackleg during his pee, so he peed like a girl for the most of the time. When he finally learned to lift the blackleg he fell over. He also had trouble to learn not to pee inside the house. Tahvo started to have some odd seizures, his eyes went back and forth and he preferred to lie down. During these seizures he reacted to my voice and could even walk to another place to lie down on. The nystagmus could at the most severe seizures continued for hours. During these severe seizures he usually also started to vomit heavily. During these seizures we took him to the veterinarian, and every time they told us that it did not seem like an epileptic seizure but they could not tell us what it was. Every blood sample was normal. At one point they suspected Tahvo had been eating something that he reacted to buy vomiting and his eyes started because of
that to move from side to side.
Last fall Tahvo got so clumsy and seemed to walk with his spine like an arrow. We took him to an Orthopedist and they found nothing wrong in the x-rays of his hips and spine. The Orthopedist told us Tahvo was suffering from ataxia in all of his legs, and he suspected a neurological disease surpassingly in the cerebellum. At this time the reflexes in Tahvo´s blacklegs and the corrections of the position of the blacklegs were appreciable delayed. We took Tahvo home and he seemed to be a happy dog, with his small defects, for a while. But a turn to the worse took soon place. Tahvo got scared of people and got also unpredictable and did not approve strangers and strange dogs to come near him. He even started to growl at people. He even tried to attack a dog and it seemed that he would have bit the dog if he could have reached out to it. He could get scared of something so intensively that he started to walk in circles very nervously even though I did not see anything that could had scared him off that badly. Beside all these symptoms Tahvo could not cope to be left alone in the house. We have taped his sounds during a day alone at the house. On the tape you could hear him walking around restlessly and hauling the whole day. He calmed down when I came home. Tahvo was always a very small sized lagotto, he only weighed 11 kg, and he had never a good appetite. Kiia arranged an appointment with Tarja Pääkkönen DVM, Dipl ECVN at The University of Helsinki and the clinical examinations showed ataxia in the legs and at this time the reflexes in Tahvo´s blacklegs and the corrections of the position of the blacklegs were even more delayed than before. The MRI-scan showed some defects at the cerebellum and we got the crashing news that this was probably Cerebellar Abiotrophy and he got a calculated time of six months to one year of living. The MRI-scan also showed that the brain chambers were bigger that suspected. We went home with the fact that my dog has to be putted to sleep in a very short time. This was devastating for me. But I never forget the staff at The Helsinki University. They really were very friendly and understanding all the time, professionals, but they really cared of my feelings and understood that I did not understand and they explained over and over again, tactfully, the situation. The dog was a member of my family and the thought of losing him hurt so much. Kiia has stood by my side during the whole sad story and done everything in her power. Nobody could have done more. I hope that my Tahvo and his brother Remu can make a difference for every other Lagotto in the future and keep other Lagottos healthy so the breed can go on and give joy to their owners. This should be all our Lagotto owners’ priority to care about the breed in the right way and to be open and not hide illnesses. Tahvo was euthanized in January 2013 at The University of Helsinki and the group of Dog Genetics Research group got his remains and the histopathology exam shoved that Tahvo had The Storage Disease”
As I told you in the beginning of this writing about me having also the first pathologically researched lagotto with Cerebellar Abiotropy in 2003. I will write you this story as well, because as you all noticed the symptoms are alike Storage Disease, but now there is a way of getting the right diagnose for The Storage Disease by DNA-test and the dog has not to be euthanized to get this diagnose, but Cerebellar Abiotropy still requires autopsy to get the diagnose. The main symptom of cerebellar abiotrophy is ataxia, but ataxia can also be caused by other diseases or intoxication. Basicly, as there is degeneration of cerebellar cortical cells in abiotrophy, full recovery is not possible but typical course for the cerebellar abiotrophy is either slowly or rapidly progressive. I can tell you that my Vilmas litter-sister had Cerebellar Abiotrophy and lived with it for ten years. Other cerebellar diseases can be mixed with this condition and that's why it is always very important to get histopathological confirmation for the disease. For us researchers the most valuable samples are blood for DNA extraction and also histopathological brain samples (as this condition can only be confirmed histopathologically ). The complete diagnosis of cerebellar abiotrophy requires both neurologist and pathologist. There are skilful persons both in University of Helsinki and University of Bern who can help and contact veterinarians/ neurologists/ pathologists in other countries as well. The population of Lagottos is small worldwide, so every confirmed case is very valuable for the research. In addition, blood samples from healthy relatives are collected both in Bern and in Helsinki. The pedigree information is also important; the researchers need to know how dogs who participate to the study are related to each other. So far the number of samples with histopathologically confirmed Cerebellar Abiotrophy diagnosis is small, but they have started to search for the gene(s) causing Cerebellar Abiotrophy. The research is ongoing and no preliminary results exists yet. Instructions for sample submission and participation can be asked from eija.seppala@helsinki.fi (geneticist in the University of Helsinki; www.koirangeenit.fi) tosso.leeb@vetsuisse.unibe.ch (professor in the University of Bern)
Once more…the sad story of my Vilma-lagotto…Published first in 2003... Punatassun Nebulosa AC, or Vilma as we used to call her, was born 7.12 2002 and passed away 7.4 2003 suffering from Cerebella Abiotrophy. They treated Vilma at The Helsinki Univesrity department of veterinary medicine. Here she also was euthanized and they did do a histopathological examination, as well. “Hi to all Lagottos and Lagotto people. I´m a chick called Vilma, and I´m 4 months old. I live with my Mum, dad and two human-sisters. They have made the backyard all for me and my needs. Mum doesn´t even get mad if I´m playing the gardener with her, what they used to call, flowers. But the best of all is our summer cottage. There I´m free to explore the mystery of the earth. The summer has just begun, so I have a lot to explore. It was at the summer cottage mum noticed that there was something really wrong with me. Dad was up North in Lapland snowmobiling. Mum and I had helped out granny carrying out wood from the forest and mum thought at first that I was too tired, my blacklegs did slip and shake. But the condition got worse on Sunday when we got home, I started to fall over. At first they blamed I got so much worms in my belly, but mum had already given me medication for that. So mum took me to the veterinarian, as worried as she was. The veterinarian examined me properly, and as I was her first Lagotto-patient she didn´t argue with the information of the worms by the breeder and put Stronghold-medicine in my neck to prevent worms. She did, though, talk about something like a need to see a neurologist if I didn´t get any better in a couple of days. I didn´t worry a thing, the vet was a really nice person, she told me I was a very brave and nice little doggie, and I just LOVE people. Dad got home and I was thrilled. He always takes me with him to the sauna and I love it. But now I couldn´t manage to get all the way up to the seats, but dad helped me as nice as he is, and we had a great time in the hot sauna. I had already learned what the refrigerator-door sounded like. So nobody could open it without me nearby. I was that guard, you know. Mum and dad got sometimes a little nervous with me hanging around the fridge all the time. I can already do "my things" outside. You should know how proud they are!
So I don´t have to read the old newspapers by the door anymore. The problem with me, you see, is that I don´t have the balance like you other Lagottos. I try to play and run but always fall to the ground. Mum is afraid I might broke a leg someday. My whole body is shaking and it´s a big job to try to stand up without falling all the time. Mum took me back to that nice veterinarian, because I got worse. I was just so happy seeing her again. But she was very sad and the next day we went to The Helsinki Univesity pet-hospital to see a neurologist. So off we went the very next day by car. The neurologist was a really nice guy, even though they spoke English, and I just understand Finnish, you see. The neurologist examined me by different methods, walking, running and the best was that I saw a BIG horse, too. Dad was also with us. The neurologist told mum and dad that I had some problems with my cerebellum. They came to the conclusion that I had to spend the night at the hospital and they´ll run some tests and take a MRI-scan out of my brain. The very next day the bomb exploded! I had Cerebellar Abiotrophia, and there´s no cure for this, and nobody knows how it proceeds. So I can never ever be a normal Lagotto... My family was devastated, even though I was thrilled of going home, home sweet home. My tail almost broke as much I had to move it in the happiness I felt. This disease hasn´t changed my mood at all. I can do a lot of tricks. I´m still a Lagotto, you know... I just can not do everything. Now we are waiting and observing my condition. The last couple of days has been horrible. I can´t even do my pee without some help from mum or dad. Thank God, they help me out, otherwise ... Eating has become difficult as well. I´m falling in to the food cup. Nothing does matter as long as my family loves me! They are going through a very hard time as well, and I do try to cheer them up. They have to laugh at me, as silly as I can be. But the atmosphere at home is sad. They are crying a lot. Today we went back to the neurologist and they made some more examinations. They calmed me down with drugs...mummy kissed me goodbye and held me for the last time... Now I´m playing up here in Dogs Heaven. I am no long a sick Lagotto!!! I just feel so bad for my family...they DO miss me. I send Lagotto-greetings to you all, Vilma”
...here is the final report on Vilma...
History: abnormal gait since about 3 weeks. General clinical and orthopedically examination: normal. Neurological examination: generalised ataxia, hypermetria in the front, deficits in the postrual reactions, normal reflexes, decreased menance reaction on both sides. Blood examination: normal. Magnetic reconance imaging: the cerebellum seems to be somewhat smaller as expected; hypointense areas in T2 in the white matter of the cerebellum and mesecephalon; these changes seems to be symmetrical and do not enchance after the gadolinium aplication. These lesions are isointense or even mildly hypointense in T1. Cerebrospinal fluid examination: normal. Necropsy: the cerebellum weighed about 7% of the total brain (normal 10-12%). No lesions were found in any of the brain or spinal cord parts except the cerebellum. Here there is a profound loss of the granular layer. This lesion is through all of the folia of the vermis and paravermis and the medial part of the lateral aspect of the hemisphere but the most lateral folia of the hemisphere are spared bilaterally. Histopathological diagnosis: cerebellar abiotrophy Conclusion: described degenerative cerebellar disorders in Vilma most likely have an inherited pathogenesis as it is described in other dog breeds.
A short conclusion of the Storage Disease:
The results of the genetic study indicate that the Lagotto Storage Disorder in inherited through a single gene, in an autosomal recessive manner. In recessive disorders, the affected dogs have inherited two copies of a disease-causing gene mutation. All dogs inherit one copy of each gene from their dam and one copy from their dire. Those Lagottos that receive a NORMAL result have inherited two normal copies of the discase gene. Their risk of being affected I minimal and they do not pass the mutation down to their offspring. CARRIER dogs have inherited one normal copy and one with the mutation. Their risk of being affected I also minimal but they pass the mutation down to approximately half of their offspring. If a carrier dog is used for breeding, it should be mated with a dog that has been tested as normal. In carrier/carrier –mating, the resulting offspring can be either affected, carrier or normal, whereas in carrier/normal –mating, only carrier or normal dogs are born. AFFECTED dog have inherited the mutation from both parents, and do they have two copies of the mutation. Their risk of developing the disease is very high. It is not recommended to use affected dogs for breeding.
Please feel free to contact me if anything in my writing seems odd or you do not understand what I have tried to tell you. I ment to keep the text as uncomplicated as possible.
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