Australian Shepherd Health & Genetics Institute

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The Deceivers

Easily Misdiagnosed Hereditary Diseases 

by C.A. Sharp

First published in Double Helix Network News, Spring 2008, Rev. May 2013


A young Aussie goes blind for no apparent reason.
An eight-month-old pup has severe and ultimately fatal seizures.
A formerly even-tempered bitch becomes dangerously aggressive.
A five-year-old altered male dies of probable warfarin poisoning.
A breeder repeatedly finds himself faced with abnormally small litters.

All of these cases have something in common:  The cause may not be the obvious thing.  Jumping to a conclusion based on personal experience or what you know to be common in the breed may be mislead you.   Even veterinarians can sometimes be fooled.  They base their findings on examination of the dog and tests results, pursuing the most probable diagnoses if the results aren’t clear-cut.  In most cases the vet or a knowledgeable breeder will be right, but sometimes a rare condition—or even a common one with non-specific symptoms—will deceive them.

Some of these “deceivers” don’t merely evade diagnosis.  Those that are also hereditary may lead a breeder to make decisions that could significantly impact her breeding program.  Initial signs of a deceiver disease may be vague or intermittent, so the dog’s owner doesn’t realize that something serious is going on.  Symptoms may overlap with one or more other diseases.  Definitive diagnostic tests aren’t always available and, if they are, they may not be part of a standard testing regimen.

It is important to know which hereditary deceivers are most likely to occur in Australian shepherds.  Knowing what they are and what to do if you suspect them can be important for your breeding program, your dogs’ health and, in some cases, their lives.

A cast of bad characters

I have been tracking hereditary diseases in Aussies since the 1980s.  I have encountered several that may be mistaken for more common problems.   Some appear to be no more than a stroke of bad luck or due some unknown environmental cause.  As a result, you may not discuss it with your vet in a timely fashion.  Some deceivers may mislead you and your vet because they are so similar to other diseases.  Your veterinarian may figure it out, but if you can suggest what might be happening with an intractable illness, your dog could get needed treatment sooner.  A couple of these deceivers—the really bad actors—may not give you or your vet much time to solve the mystery.

The hereditary diseases listed below are those I have found most likely to deceive us.

PelgerHuët Anomaly (PHA)

PHA causes abnormalities in the neutrophils, a type of blood cell.  The incompletely dominant gene that causes PHA is lethal to puppies that inherit two copies.  The parents, who have only one copy, will be healthy but exhibit minor blood anomalies.  The inheritance of PHA is similar in some ways to the mutation that causes merle:  Once copy is fine and dogs with it can be identified by phenotype—coat color for merle and a blood test for PHA—but two copies cause severe defects.

When two PHA positive dogs are bred the litter size will be abnormally small because the puppies with two copies of the mutation will be reabsorbed before birth.  Not every small litter is the result of PHA, but it should be considered a possible cause if the small litters only happen occasionally.  It won’t happen every time; only when two PHA positive dogs are bred together.  Don’t assume the occasional small litter is a matter of bad luck or something having gone awry with the breeding.  It might be PHA.

While false-negative results on the test are possible, it will usually tell you if your dog is PHA-positive. If it is, you can avoid small litters by the simple expedient of breeding only to PHA-negative mates.

Autoimmune Thyroiditis

Once can make a good argument that hypothyroidism, below normal thyroid hormone levels, is one of the most frequently misdiagnosed canine diseases.  It is a very common canine disease, but currently available tests are not conclusive and the symptoms of the disease are highly variable and not specific to hypothyroidism.  It is a disease that is easy to both under- and over-diagnose.

Absent any clinical findings typical of thyroid disease, is the dog actually sick?  Even with apparently positive test results, you should not assume the dog has the disease.  When there are apparent symptoms, they can be shared by a number of other diseases, or even behavior problems.  A dog with thyroiditis may seem tired, dull witted or unreasonably aggressive.  It can get fat.  Its coat and skin may be bad.  It can have digestive or reproductive problems.  It may be cold intolerant.   Hypothyroid dogs may exhibit one or several of these signs, but so do dogs with a plethora of other diseases, some hereditary and some not.

Just to put icing on the cake, hypothyroiditism may induces a secondary disease—an illness triggered by another disease.  The secondary diseases that arise may also occur independently, so it is important to determine whether or not thyroid disease is implicated.  Corneal degeneration (which may be identified as corneal dystrophy, which can be inherited) is a disease of the eyes; von Willebrand’s Disease, a bleeding disorder, and testicular atrophy are among the secondary diseases you may see in association with hypothyroidism.  Each can be separately inherited, though they are rare in Aussies.

Autoimmune thyroiditis, a form of hypothyroidism, is inherited.  Any dog with positive TGAA levels in a thyroid test panel has this disease.  However, if testing is delayed until a dog is 7 or more years of age the immune system may already have destroyed the thyroid gland and no TGAA will be present.

Other Autoimmune Diseases

Thyroiditis isn’t the only autoimmune disease that can be misdiagnosed.   This class of diseases arises because the immune system targets body tissues as if they were foreign invaders.   There are numerous different autoimmune diseases and their signs are often non-specific, overlapping with each other and with other kinds of disease.  Lupus, one of the most common in Aussies, can cause skin problems, particularly around the face.  But so can pemphigus and dermatomyositis.  Dogs with lupus may also develop a secondary case of autoimmune hemolytic anemia, which can be a primary disease.

Idiopathic thrombocytopenic purpura (ITP) or thrombocytopenia, presents signs similar to warfarin (rat) poisoning.  Standard treatment for warfarin poisoning will not help a dog with ITP and may make it worse.  Internal bleeding might also be a sign of hemangiosarcoma (see below,) a cancer common in Aussies.

Uveodermatological syndrome, sometimes called Vogt-Koyanagi-Harada-like syndrome or VKH, initially impacts vision.  Later, the coat and skin of affected dogs will lose pigment.  Before that happens, you may think you are dealing only with an eye problem.  Some dogs develop secondary myasthenia gravis (MG.)

MG also occurs as a primary disease.  Affected dogs lose receptors for a chemical messenger called acetylcholine, which signals skeletal muscles to contract.   Early on, an affected dog appears to lack stamina, which can delay diagnosis and treatment if the owner assumes it is out of shape or unmotivated. Some dogs with MG develop secondary megaesophagus, leading to extreme difficulty eating and a high risk of aspiration pneumonia.

Diagnosis of inflammatory bowel disease (IBD) can be difficult because the disease may affect any part of the digestive system and cause a variety of gastro-intestinal problems which may also be due to other diseases.


Hemangiosarcoma (HSA)

HSA is our breed’s #1 cancer is a cancer of vascular tissue, the stuff of which blood vessels are made.  Dogs sometimes appear completely healthy and suddenly become very ill or die suddenly when an undetected tumor bursts and the dog bleeds out.  If a necropsy is not performed, the way in which it died may be confused with warfarin poisoning, a stroke, or cardiomyopathy.  Stroke would only be expected in elderly dogs and cardiomyopathy is extremely rare if not totally absent in Aussies.

If an apparently healthy dog suddenly sickens and dies or drops dead, particularly if it is not elderly, having a necropsy performed to determine the cause is advised.  The pedigree data gathered in the ASHGI cancer survey has indicated a familial pattern to this disease so it is important for breeders to know if what a dog actually died of was HSA.

Multi-drug Reactivity 1(MDR1)

MDR1isn’t a disease, it’s a gene.  A mutation of this gene confers extreme sensitivity to a variety of medications, some of them very common in veterinary practice.  The frequency of the mutation is extremely high in Aussies and Minis.  Not knowing a dog’s genetic status can result in severe or even fatal drug reactions that may sometimes be attributed to another cause.  There is a genetic test and every Aussie, Mini, or mix of either breed should have that test unless it is out of two tested-clear parents.

 Cobalamin Malabsorbtion

Having two copies of a particular gene mutation will prevent a dog from absorbing Vitamin B12, or cobalamin.  Cobalamin malabsorbtion is a metabolic disease.  Symptoms usually begin around 6-12 weeks of age, but may not start until young adulthood.  They include poor appetite, lethargy, failure to thrive, wasting, vomiting, seizures, or general ill-health. The most serious complications include abnormalities of the blood and nervous system that are lethal if untreated. It is common for B12 deficiency to be mistaken for another disease because of the varied clinical signs.  It can mimic liver shunt, early-onset epilepsy and some immunodeficiency diseases.

Cobalamin malabsorbtion can be secondary to other diseases, like exocrine pancreatic insufficiency.  It is important to know whether the disease is primary and hereditary or secondary to something else.  There is a DNA test for hereditary cobalamin malabsorbtion.

Neuronal Ceroid Lipofuscinosis (NCL)

NCL is a degenerative neurological disease.  As with VKH (above) the first thing an owner notices may be vision loss.  It will be followed by more serious neurological problems affecting both mobility and disposition.  The dog may have seizures, and in a breed where epilepsy is rampant it might be mistaken for that disease.  A vet treating an NCL dog would be unlikely to make that error though correct diagnosis may still prove difficult.  Ultimately the disease is fatal.  The only way at present to positively diagnose NCL in an Aussie is with a necropsy sample of brain tissue.  There is a DNA tests for a form that was found in one Aussie, but that dog had no known pedigree so we can’t know who might be related and it is possible that Aussies might also have one of the several other forms of this disease, some of which have DNA tests.

Since we are so attuned to epilepsy in Aussies, we tend to equate major seizures with that disease.  We must learn to distinguish between those seizures that are due to primary epilepsy and those with other causes, like NCL, if we are to make informed breeding decisions.

Check it out

For the sick dog’s sake, arriving at a proper diagnosis is important.  If the dog has one disease and it winds up being treated for something else, the disease may not respond to the treatment.  In some cases (ITP vs. warfarin poisoning or severe cobalamin malabsorbtion mistaken for intractable epilepsy or a liver shunt) the mistake may prove fatal.

Cobalamin malabsorbtion is often misdiagnosed.  It is virtually unknown among dog owners and breeders and not well known among veterinarians.  Nor is the fact that there are both diagnostic tests and a DNA test available.  As a result, the affected dog may be treated for any of a number of other diseases without success when a regular regimen of B12 injections will return it to health in short order and keep it there.

NCL is also little known, but getting a presumptive diagnosis may result in better supportive care for the dog and cue the breeder to hold off breeding relatives until a necropsy determines the whether it actually was a case of NCL.

Autoimmune diseases can be positively diagnosed, though sometimes it takes a while to do it.  Some things, like MDR1 ought to be assumed until ruled out.  This is the owner’s or breeder’s job since the test is sold direct to the public.  If your dog has the MDR1 mutation your vet should be provided not only with the test results but with a list of the drugs to which your dog may react.

If your dog is ill and showing symptoms that may indicate any of the deceivers listed in the prior section, suggest the possibility to your vet.  The dog may not have one of those diseases, but it is important to know whether it does or not.   Misdiagnosis can lead you to breed a dog that has or carries an inherited disease because you think the problem was acquired, or to breed a relative to another risky dog because you don’t realize what the affected dog really had.

Prevention is worth a pound of cure

There are things breeders can do to head off some of these problems before they happen.  There are DNA tests that will tell you if our dog is at risk for multi-drug sensitivity or cobalamin malabsorbtion.  PHA positive dogs can be diagnosed with a simple blood smear.

Properly identifying affected dogs and, where possible, determining the genotype for relatives, is vital to prevent producing more affected pups.

Since the diseases discussed here are inherited or, in the case of the autoimmune diseases, genetically predisposed, affected dogs generally should not be bred.  There are two exceptions:  MDR1 and PHA.  The medications to which an MDR1 dog reacts are not part of the natural environment; the important thing is not to give the dog any of those drugs.  Presence of the mutation should be considered faulty, however, and efforts made to breed away from it.  PHA positive dogs can live normal, healthy lives but you do need to avoid breeding them to each other if you want to get normal-sized litters.

Where testing is available, use of the tests will tell you what you are dealing with on a genetic basis.  You can breed dogs with the MDR1 mutation, PHA or carriers of cobalamin malabsorbtion to dogs that have been tested clear.  By giving preference to the clear offspring of the carriers, the frequency of the mutations can be reduced over time and several generations.

Not every Aussie needs to be screened for these diseases.  Only MDR1 is so common that every dog should be tested.  The PHA and cobalamin malabsorbtion tests only need to be used if a dog may have the diseases or a relative was affected and you need to determine your dog’s genotype.

For those diseases that lack carrier screening tests, once a case has been diagnosed the affected dog should be withdrawn from breeding.  The parents should not be bred to each other again or to any other dog with a family history of the disease.  In the case of the autoimmune diseases, all forms should be considered as a group, not individually; one can lead to another and different types will run in the same family.

Always keep the deceivers in mind.  If your dog may have one of these diseases, work with your vet to get it properly diagnosed.  If it does have one, let the owners of related dogs know and apply the information to your breeding decisions.  By working together with our vets and each other, we can keep from being fooled.