The author would like to thank Dr. Urs Giger, University of Pennsylvania, for discussing the disease with her and pointing her toward additional resources.
It started with a phone call. Not the first, but the second Maureen had received in two weeks: A 10-month old Australian Shepherd puppy from her last litter was seriously ill. This one was having seizures and the owner’s veterinarian didn’t know if the puppy could be saved. The first call had also been about a very sick pup. That one, who had been the liveliest in the litter, wasn’t growing. He was lethargic and disinterested in food and the treating veterinarian had not yet figured out what was wrong. More tests had been ordered.
Maureen was stunned. Having two puppies from the same litter but in different homes become so seriously ill almost at once was devastating…and extremely unusual. Maureen suspected the pups’ illnesses might have something in common. She asked that the owner of the seizing pup, who lived in the next town, bring the puppy to her vet for a second opinion. Maureen brought her vet’s staff up-to-date on what had been going on with both pups and made an appointment.
Maureen’s vet was stumped at first, too. Then it occurred to him that what Maureen and her puppy owner described was similar to something he’d seen in another breeder-client’s pups. Only those dogs were Giant Schnauzers. After discussing it with Maureen and the seizing puppy’s owner, he collected a urine sample and sent it to the University of Pennsylvania for analysis. His hunch paid off: The seizing puppy did not have epilepsy or any other neurological disease; it had hereditary cobalamin malabsorption (HCM.) He started treatment immediately. Maureen advised her other puppy owner of the findings, so that puppy could be screened as well. It also was found to have HCM. Within a couple weeks, both pups were back to normal.
HCM is easy to treat, but easily can be misdiagnosed or unrecognized for what it is. Recently, another young Aussie was identified as having HCM. It became extremely ill. That pup’s veterinarians felt he might be at risk of dying and, among other things, they did an exploratory abdominal surgery to determine what was going on. Only later did they realize it was cobalamin malabsorption. The pup is now doing fine, though he does have a surgery scar to brag about.
HCM is unknown to almost everyone in Australian Shepherds, as well as the veterinarians treating our dogs. The author, who has been following and writing about genetic health issues in Aussies since the early 1980s, first learned about HCM last summer when she followed up on a breeder’s report by contacting the University of Pennsylvania for information.
The research that first recognized cobalamin malabsorption could be inherited was done in 1991. HCM is caused by a mutation a gene called Amnionless (Amn.) The responsible gene was identified in 2004. The mutation is most commonly associated with Giant Schnauzers, though they are not by any means the only breed to have it. It also occurs in Shar Pei, Border Collies, Beagles, Australian Shepherds, and probably others.
Dogs that inherit two copies of the Amn mutation, one from each parent, will have HCM. It is a serious and potentially life-threatening metabolic disease. Signs usually start around 6-12 weeks of age, but may not be noted until the dog is an adult. The lining of the lower intestine of affected dogs does not absorb vitamin B12. B12 is necessary to proper metabolic function and lack of it can impact a number of organs.
In the clinic
Because HCM prevents the body from absorbing B12, the disease can cause a wide range of clinical problems, including lack of appetite, lethargy, failure to thrive, wasting, vomiting, seizures, or general ill-health. The most serious and potentially life-threatening complications include abnormalities of the blood and nervous system. The signs can mimic those of liver shunts, early-onset epilepsy and some immunodeficiency diseases. HCM might be mistaken for another disease in Aussies not only because of the varied clinical signs, but also because some of those diseases are more common, HCM is not generally recognized as breed health issue, and some vets may not be aware of HCM at all.
Some of the things HCM can mimic, like epilepsy, are very common. Cobalamin malabsorption can be secondary to other diseases, like exocrine pancreatic insufficiency (EPI) which is rare in Aussies but has a “higher profile” among veterinarians. It isn’t surprising that vets might mistake HCM for something else.
If a veterinarian performs standard diagnostic tests on a dog exhibiting any of the signs mentioned above, the results may show low counts of red and white blood cells, platelets and neutrophils, excess blood ammonia, and protein in the urine. If test results indicate the above abnormalities, it would be wise to test for HCM. The diagnostic tests available are less invasive and expensive than the more advanced forms of testing that might be used to rule-out other conditions. If HCM test results are negative, other appropriate tests and procedures can follow.
Fortunately, with proper diagnosis and relatively inexpensive treatment, affected dogs can be kept in remission throughout their lives. HCM dogs must receive subcutaneous vitamin B12 injections every 2-4 weeks for life. Response to initial treatment is rapid and results will be seen in a matter of days. Serious cases may require more intensive B12 therapy and supportive care for up to 10 days.
Texas A&M offers a blood test that determines serum cobalamin. However, the levels revealed by this test may not be diagnostic. The University of Pennsylvania’s methylmalonic acid (MMA) test looks for the accumulation of this abnormal metabolite in a urine sample. (Note for veterinarians: The sample must be shipped on ice overnight.)
While the above tests can help in properly diagnosing an HCM dog, they don’t tell breeders which dogs are normal carriers of the mutation. Fortunately, there is already a DNA test available through the University of Pennsylvania. Results are confidential and will be provided only to the owner or veterinarian. This test will identify not only carriers, but affected dogs before they exhibit signs of the disease. With early identification, treatment could start at once so health complications can be avoided. With proper use of the test, carrier dogs could still be used for breeding to preserve their desirable traits without ever producing another affected puppy.
Primary cobalamin malabsorption (HCM) is hereditary. At this point frequency of this disease in Aussies is unknown, but cases have been identified over the past decade in various parts of the US as well as abroad. It could have a devastating impact a breeding program and mislead the breeder into thinking she was dealing with other, more frequently seen or better-recognized hereditary problems like epilepsy or exocrine pancreatic insufficiency.
It is very possible that some of the intractable, early-onset (under a year of age) cases of epilepsy reported in Aussies were actually HCM. Since there is no positive diagnostic test for epilepsy at this time, diagnosis is made by ruling-out other possible causes. HCM testing should become part of the standard battery of tests administered to Australian Shepherds during that process.
Liver shunt, another common misdiagnosis in seriously ill HCM dogs, is not common in Aussies at all. The author is suspicious that those few cases of liver shunt which have been reported to her were actually HCM. Any time liver shunt is suspected in an Australian Shepherd, HCM should be ruled out as soon as possible if for no other reason than to avoid an unnecessary surgery. Improper diagnosis of HCM-affected dogs can also lead to unnecessary euthanasia.
What to do
The Australian Shepherd Health & Genetics Institute, Inc. (ASHGI) has been in contact with the University of Pennsylvania and will be following this disease in the breed. ASHGI has made information for breeders and owners available on their website. They would also like to track specific cases to create a database on affected and carrier dogs. Interested dog owners can do this through ASHGI’s International Directory for Australian Shepherd Health (IDASH). Data may be designated confidential or may be shared in the open health database.
If you have puppies or young dogs that are displaying any of the signs listed above, ask your veterinarian to consider possible HCM. When cases are identified, notify the owners of both parents as those dogs will be carriers. If you learn your dog is a carrier, DNA test any first-step relatives who may be bred to determine their status. “First-step” relatives are parents, offspring and siblings. Identifying possible cases of HCM and using the diagnostic and DNA tests will help prevent the production of more affected puppies. It can also save lives.
Finally, but just as important as the above actions, report your HCM DNA test results to the Orthopedic Foundation for Animals using OFA’s “DNA Based Genetic Disease” application form. It can be downloaded from their website.
We don’t know how common HCM is in Australian Shepherds. It might not be common at all. Even so, keep it in mind if your dog is having any of the symptoms described above and make sure your veterinarians know that HCM is present in Aussies. Failure to recognize it can cause needless suffering and expense, or even the life of someone’s beloved dog.