L-2-HGA – Information taken from AHT Website on 16/07/05 @ 06:52.

L-2-HGA (L-2-hydroxyglutaric aciduria) in Staffordshire Bull Terriers is a neurometabolic disorder characterised by elevated levels of L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid.

L-2-HGA affects the central nervous system, with clinical signs usually apparent between 6 months and one year (although they can appear later). Symptoms include epileptic seizures, "wobbly" gait, tremors, muscle stiffness as a result of exercise or excitement and altered behaviour.

The mutation, or change to the structure of the gene, probably occurred spontaneously in a single dog but once in the population has been inherited from generation to generation like any other gene. The disorder shows an autosomal recessive mode of inheritance: two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease. Individuals with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring. When two apparently healthy carriers are crossed, 25% (on average) of the offspring will be affected by the disease, 25% will be clear and the remaining 50% will themselves be carriers.

The mutation responsible for the disease has recently been identified at the Animal Health Trust. Using the information from this research, we have developed a DNA test for the disease. This test not only diagnoses dogs affected with this disease but can also detect those dogs which are carriers, displaying no symptoms of the disease but able to produce affected pups. Carriers could not be detected by the tests previously available which involved either a blood or urine test detecting elevated levels of L-2-hydroxyglutarate or magnetic resonance imaging. Under most circumstances, there will be a much greater number of carriers than affected animals in a population. It is important to eliminate such carriers from a breeding population since they represent a hidden reservoir of the disease that can produce affected dogs at any time.

The test is available now and information on submitting samples is given below.
Breeders will be sent results identifying their dog as belonging to one of three categories:

CLEAR: the dog has 2 copies of the normal gene and will neither develop L-2-HGA, nor pass a copy of the L-2-HGA gene to any of its offspring.

CARRIER: the dog has one copy of the normal gene and one copy of the mutant gene that causes L-2-HGA. It will not develop L-2-HGA but will pass on the L-2-HGA gene to 50% (on average) of its offspring.

AFFECTED: the dog has two copies of the L-2-HGA mutation and is affected with L-2-HGA. It will develop L-2-HGA at some stage during its lifetime, assuming it lives to an appropriate age.

Carriers can still be bred to clear dogs. On average, 50% of such a litter will be clear and 50% carriers; there can be no affecteds produced from such a mating. Pups which will be used for breeding can themselves be DNA tested to determine whether they are clear or carrier.

Samples for testing (3mls blood in an EDTA tube), should be sent together with a completed DNA Testing form and a cheque for £60-00 (inc VAT) for each sample to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU. DNA testing forms can be downloaded from our web site ( http://www.aht.org.uk ). DNA testing forms can also be obtained by contacting Vikki Lett 01638 750659 ext 1223 or via e-mail to vikki.lett@aht.org.uk.

HC – Hereditary Cataracts – Information taken from AHT Website on 12/02/06 @ 10:16.

Hereditary Cataracts in Staffordshire Bull Terriers has been recognised as an inherited condition since the late 1970’s. Affected dogs develop cataracts in both eyes at an early age. The condition is not congenital, so the lenses are normal at birth but cataracts appear at a few weeks to months in age, progressing to total cataract (and resulting blindness) by 2 to 3 years of age.

The mutation, or change to the structure of the gene, probably occurred spontaneously in a single dog but once in the population has been inherited from generation to generation like any other gene. The disorder shows an autosomal recessive mode of inheritance: two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease. Individuals with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring. When two apparently healthy carriers are crossed, 25% (on average) of the offspring will be affected by the disease, 25% will be clear and the remaining 50% will themselves be carriers

The mutation responsible for the disease has recently been identified at the Animal Health Trust. Using the information from this research, we have developed a DNA test for the disease. This test not only diagnoses dogs affected with the disease but can also detect those dogs which are carriers, displaying no symptoms of the disease but able to produce affected pups. Under most circumstances, there will be a much greater number of carriers than affected animals in a population. It is important to eliminate such carriers from a breeding population since they represent a hidden reservoir of the disease that can produce affected dogs at any time.

The test is available now and information on submitting samples is given below.
Breeders will be sent results identifying their dog as belonging to one of three categories:

CLEAR: the dog has 2 copies of the normal gene and will neither develop Hereditary Cataract, nor pass a copy of the Hereditary Cataract gene to any of its offspring.

CARRIER: the dog has one copy of the normal gene and one copy of the mutant gene that causes Hereditary Cataract. It will not develop Hereditary Cataract but will pass on the Hereditary Cataract gene to 50% (on average) of its offspring.

AFFECTED: the dog has two copies of the Hereditary Cataract mutation and is affected with Hereditary Cataract. It will develop Hereditary Cataract at some stage during its lifetime, assuming it lives to an appropriate age.

Carriers can still be bred to clear dogs. On average, 50% of such a litter will be clear and 50% carriers; there can be no affecteds produced from such a mating. Pups which will be used for breeding can themselves be DNA tested to determine whether they are clear or carrier.

Samples for Hereditary Cataract testing only can be cheek swabs (swabs will be provided free by AHT), samples for Hereditary Cataract and L-2-HGA DNA testing together must be 2mls of blood in an EDTA tube. Samples should be sent with a completed DNA Testing Form and a cheque for £60-00 (inc VAT) per sample for Hereditary Cataract testing alone, or £100-00 (inc VAT) per sample for Hereditary Cataract and L-2-HGA DNA testing together, to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU. DNA testing forms can be downloaded from our web site (http://www.aht.org.uk).

Blood samples which have already been tested for L-2-HGA can also be tested for Hereditary Cataracts - please provide a completed DNA Testing Form quoting the Sample Number from the L-2-HGA certificate, with a cheque for £60-00 inc VAT. DNA testing forms can also be obtained by contacting Vikki Lett 08700 509144 or via e-mail to vikki.lett@aht.org.uk.

PHPV - Persistent Hyperplastic Primary Vitreous

Scientific Definition (taken from http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00183.htm)
Persistent Hyperplastic Primary Vitreous is due to the retention of elements of the foetal vascular supply to the lens, the tunica vasculosis lentis. The lesions seen are variable amounts of fibrovascular plaque on the posterior lens capsule and possible posterior cortical cataract. The effect on sight can range from nothing to blindness. Removal of the diseased lens can be complicated by any vascular involvement. Persistent pupillary membrane is of the same origin, but this time remnant strands of the anterior part of the tunica vasculosis lentis remain attached to the iris and may occasionally interfere with sight as the result of associated lens or corneal opacities. Again, any effect on sight is variable, but cataract extraction is possible, whereas corneal opacity is not treatable.
Dr Keith Barnett - HC/PHPV in the SBT (extracts of notes from Staffordshire Bull Terrier Breed Council Meeting, 28th April, 2001

Persistent Hyperplastic Primary Vitreous (PHPV): Dr Barnett said that whilst a few cases of PHPV could be found in a number of dogs, inherited PHPV is found in only a few breeds, e.g. Doberman (particularly in the Netherlands where the breed was quite severely affected with PHPV) as well as Staffords. Unlike HC, which is not congenital (i.e. not present until around 3-4 weeks of age), PHPV is congenital (i.e. is present at birth). PHPV can be identified from as early as 2-3 weeks, although a more accurate diagnosis would be obtained at around 6-8 weeks of age. Although present at birth, PHPV is not progressive except in a few isolated cases, however it is very variable in its degree of severity and can affect both eyes. Dogs suffering from mild forms of PHPV can produce offspring that are severely affected.

During questioning, Dr Barnett confirmed that both PHPV and HC could be diagnosed by the age of 12-18 months. He saw no requirement, therefore, to continue testing purely for PHPV/HC after that age if previous results had been clear. However, he did emphasise that eye tests are designed to look for all eye abnormalities that may be inherited, so it is beneficial to continue testing beyond 12-18 months to regularly check for these. He recommended testing up to any age, but particularly through the breeding cycle of the dog/bitch.

PPSC - Posterior Polar Subcapsular Cataract (PPSC)
This type of cataract is found in other breeds, and usually remains as a small, punctate cataract. It has been placed on Schedule 3 of the BVA/KC/ISDS Eye Scheme because a number of Staffords that have been through the Scheme have been found to have this type of cataract. It is advised that as this type of cataract can't be detected through litter screening, the mode of inheritance is not known and has a variable age of onset, breeding stock should be tested annually to determine that the dog is certified clear at the time of mating.

The L2–HGA Test : Scourge or Saviour?

Before you flick over the page and read something else, please hang on a second! This article is not another semi-scientific paper, nor does it seek to provide an in-depth analysis on the origins of L2-HGA. It doesn’t even go into the symptoms to any great degree! There is, admittedly, a little bit on these issues, but only for the purposes of scene setting… nothing too heavy… promise! Instead, we are looking to explore the issue of genetic testing in general, using L2-HGA as the subject in this case. We will delve into the impact of genetic testing for the Staffordshire Bull Terrier, in particular.

What is L2-HGA?

For a start, it stands for “L-2-Hydroxy Glutaric Aciduria” and it is, put simply, an horrific, progressive condition. “Progressive”, for the non-medical out there, means that it gets worse as the dog gets older. The symptoms include “wobbly gait”, epileptic seizures (more on this particular issue later), muscle stiffness arising from excitement or exercise and, as the Animal Health Trust puts it, “altered behaviour”.

At this point the author must hold up his hands; he has never had the misfortune to see a dog affected with this condition. However, for the purposes of this article, it is not necessary to be an expert in this field.

The Genetic Test

We’re determined, here, to keep this bit sensibly short. Here goes…

Non-genetic tests, such as the traditional HC/PHPV eye test, can only determine the actual physical condition of the animal, NOT its ability, or not, to pass on the condition to its offspring. In short, tests that diagnose a problem only really conclude that the animal is “affected” with a particular condition or not. Genetic testing goes further. Much further! The results of a genetic test take one of the following forms:-

Clear - The animal does not have the condition in any shape or form at all, and therefore cannot pass it on.

Carrier - The animal will pass on “the ability to transmit the condition” to at least 50% of the puppies, or more, depending on the genetic status of the other half of the pairing. He does not himself have the symptoms, nor will he EVER have the symptoms.

Affected - The animal has the symptoms, and will also pass on the “the ability to transmit the condition”.

The above is a much-simplified explanation as the author is attempting to be true to his initial promises, but it should also be noted that, in the case of L2-HGA, the following is true:-

Clear : Clear Clear puppies
Clear : Carrier 50% clear, 50% carriers
Carrier: Carrier 25% clear, 50% carriers, 25% affected
Affected? There are calculable outcomes but hang on, who would ever responsibly breed from
an animal affected with L2-HGA?

Who Should Test?

Now there’s a question!

There is a reasonably argued view that only those who have had “trouble” with this condition need to genetically test for it. The argument for this is simply that, for these people, they have never had any of their puppies ever display “affected” symptoms and therefore they must not have a problem in their lines. This is based on the fact that with any inter-breeding, if carriers are present in the lines then, at some point, a mating involving two carriers will occur and, as seen above, 25% of the puppies (on average) will exhibit L2-HGA.

The trouble with this argument, though, is more fundamental than this; to be 100% sure, you need to know, 100%, every genetic status of every animal in every pedigree in your lines. Even in the youngest kennels, this is virtually impossible. Also, and relating to L2-HGA in particular, how many cases of this condition have been misdiagnosed as epilepsy? After all, epileptic seizures are part of the symptom set.

The other issue, for the long-established kennel and its proprietors, is one of reputation. Every breed has its icons, and pivotal figures. It is the actions of these few, highly respected people that can shape a breed for generations to come. If a sufficiently high percentage of key figures test breeding stock (and this means, realistically, 20 or so high profile characters) then the rest of the “flock” can be shamed or encouraged into testing, too. It does not matter whether a line has carriers or not, or whether the condition is a real threat – the point of this exercise is to spread the message that the health of the breed is paramount. Whilst, privately, there is perhaps bemusement about it all, the public message is “Test – and improve the health of the breed”.

What Should Be Tested?

It is only necessary to test animals that are going to be used in a breeding programme. If you think about it, it’s obvious! What is the point in testing apparently normal animals if they are never going to be called upon to produce puppies? Their ability to pass on the “power to transmit the condition” is irrelevant if they are never going to get the chance to do so!

If Carriers to Clears cannot produce Affecteds, could I use a Carrier?

From a scientific point of view, it is true that mating an L2-HGA Carrier to a Clear CAN NEVER produce an L2-HGA Affected animal. However, this is not the true crux of the question. Should we, ethically, conduct a mating that we know will, on average, produce puppies with the potential to create health problems?

For: The argument for is that to avoid carriers would mean a shrinking of the gene pool and hence would necessitate even closer in-breeding, which would in turn expose the breed to other health issues. Also, the puppies from these matings can themselves be genetically tested and subsequently bred from responsibly or, perhaps, not at all.

Against: The argument against is simply that the breed has a sufficiently large base to allow breeders to select suitable breeding stock that are not carriers. Further, if matings with carriers ARE conducted, you have the problem of controlling the actions of the people buying the puppies – making them test is not straightforward. Of course, the breeder himself could test the puppies prior to letting them go, but then, what does he do with those found to be carriers?

It is the author’s view that the above is a matter for the individual, and in the absence of Kennel Club guidelines, it falls to us all to breed responsibly and to conduct ourselves decently when it comes to the moving on of offspring. However, it may be useful to give consideration to the following potential issues:-

1. The owners of prominent stud dogs can, by testing, set a very positive example for the breed. Further, the tested-clear stud dog can NEVER produce an affected puppy, and so even if the bitch is untested, the stud dog cannot be “blamed” for any offspring subsequently found to be carriers. In this event, if progeny are found to be carriers it has to be from the Dam side of the mating, and traceability is made that much easier. This allows the breeder to continue breeding, on the basis of sound information and genetic knowledge of lines.

2. L2-HGA could be eradicated from showing stock if we all embrace the idea. Anyone who has seen an affected animal will tell you that the price of £60 is an absolute bargain if it results in the banishing of the condition from the breed.

3. The flip-side of this is for the owner of a carrier bitch wishing to have her mated. If very few stud dogs have been tested, where this bitch go to be mated without the worry of producing affected offspring? The more stud dogs that tested, the greater the choice for breeding from carrier bitches, and theoretically, the better the breed will be as a result. It is veterinary advice that we do not avoid all carriers from breeding programmes as this will result in a shrinking of the gene pool. Without knowing the true extent of the carrier problem this is hard to fully embrace, but the general point is, the author feels, most valid.