Genetic Testing L2-HGA and HC

Why genetic testing is not optional

The Staffordshire Bull Terrier is a fundamentally healthy breed, but it carries two hereditary conditions that are both serious and entirely preventable: L2-HGA and hereditary cataract. Both are recessive, which means a dog can carry the mutation, show no sign of it for its whole life, and still produce affected puppies if mated to another carrier.

This is the crucial point that many buyers miss. A visibly healthy sire and dam prove nothing about the puppies. Only a DNA test on the parents tells you whether a litter can produce an affected dog, and since the tests have been available the two diseases have become, in responsible breeding, simply extinct. When an affected puppy is born today it is almost never bad luck: it is the consequence of a mating done without testing.

L2-HGA: what it is and how it presents

L-2-hydroxyglutaric aciduria is a metabolic disorder caused by a mutation in the L2HGDH gene. The affected dog cannot correctly break down a molecule called L-2-hydroxyglutaric acid, which accumulates in the cerebrospinal fluid and progressively damages the central nervous system.

Symptoms usually appear between 6 months and 1 year of age, occasionally later. Owners describe episodes of wobbliness and loss of coordination, tremors, muscle stiffness after exercise or excitement, behavioural changes, and in many cases seizures. Between episodes the dog can seem almost normal, which delays diagnosis and gives false hope.

There is no cure. Management with a modified diet and anticonvulsants can reduce the frequency of episodes, but the condition is progressive and the outlook is poor. For a family who has raised a puppy for a year, it is a devastating diagnosis, and it costs both emotionally and financially for as long as the dog lives.

The symptoms

Signs usually appear between six months and the first year of life, occasionally later. They include:

• Epileptic seizures, often the first thing an owner notices
• Ataxia — loss of coordination
• Tremors, particularly when the dog is excited or under stress
• Muscle stiffness
• Difficulty learning, and changes in behaviour
• Exercise intolerance

The disease is progressive and incurable. Affected dogs have a badly compromised quality of life and are frequently euthanised on humane grounds. There is no treatment, only symptomatic management of the seizures — and that is the point: this is an entirely preventable condition, and no puppy should ever be born with it.

Hereditary cataract: what it is and how it presents

Hereditary cataract in this breed, caused by a mutation in the HSF4 gene, is not the age-related cataract seen in older dogs of any breed. It appears early, typically between 4 months and 3 years, and it is bilateral and progressive.

The lens becomes progressively opaque and the dog loses sight, usually completely, often before its third birthday. Surgery can restore useful vision in selected cases but is expensive, is not always successful, and requires a specialist ophthalmologist. Again, the disease is entirely avoidable by testing before the mating rather than treating after the diagnosis.

The symptoms

Hereditary cataract in this breed develops young, from one or two years of age, unlike the senile cataract of old dogs. What you see is:

• Visible clouding of the lens — the eye looks veiled or whitish
• Progressively failing sight
• The dog bumping into things, or hesitating in poor light
• Complete blindness in advanced cases

Unlike L2-HGA, cataract can be operated on with good results, but surgery is expensive and the aftercare is demanding. Prevention through testing remains by far the better route.

How the tests work

The tests are DNA based and straightforward. A cheek swab or a small blood sample is taken, ideally by the veterinarian who also verifies the dog's microchip so that the sample is unambiguously linked to that animal, and sent to an accredited laboratory. The result arrives within 2 to 4 weeks and is valid for life: the DNA does not change, so a dog is tested once and never again.

Costs vary by laboratory and country, but for both tests together expect something in the region of around 120 euros for the genetic panel at the laboratory, rising to roughly 400 per dog once you add the veterinary sampling, the shipping and the eye examination. Compared with the cost of a lifetime of anticonvulsants, or of cataract surgery, or of the grief of a family, it is a trivial figure. It is also the reason no serious breeder considers it a discretionary expense.

Where the testing is done

The main laboratories carrying out these tests are the Animal Health Trust in the UK, which developed both of them and is now part of The Kennel Club; Laboklin, the German laboratory that also operates in Italy; Optigen in the United States, specialised in eye conditions; and Embark, whose broad panel includes L2-HGA and HC.

The sample is a cheek swab or a blood draw taken by a vet, sent to the laboratory, and the certificate comes back with the dog's microchip number on it. That number is what ties the result to a specific animal — a certificate without one proves nothing about the dog in front of you.

Reading the results

Clear means the dog has two normal copies of the gene. It cannot develop the disease and cannot pass the mutation to its offspring.

Carrier means the dog has one normal copy and one mutated copy. It will never develop the disease itself, and it is not a defective animal: a carrier of excellent type and temperament is a perfectly legitimate breeding dog, provided it is only ever mated to a clear partner. Every puppy from such a mating is healthy, though half of them will be carriers in turn.

Affected means two mutated copies. The dog will develop the disease and must never be bred.

The single rule that makes the arithmetic safe is this: carrier to carrier must never happen. That mating produces, statistically, one affected puppy in four. Everything else is manageable.

The arithmetic of a mating

The two middle rows deserve a note, because they are the ones people argue about. Technically they produce no affected puppies, which is why some breeders consider them acceptable. But they leave carrier puppies in circulation, in families that may one day breed them with another carrier: the problem is not solved, it is moved one generation down and handed to someone else. At Del Piccolo Diavolo carriers are not bred, and the only mating we consider is the first row of the table.

The last row is the whole reason the tests exist: two healthy dogs, mated together, produce one sick puppy in four.

Testing by parentage

You will often see a pedigree stating that a dog is clear "by parentage" or "hereditarily clear". This means the dog itself has not been tested, but both its parents were tested clear, which makes it genetically impossible for the dog to carry the mutation.

This is legitimate and accepted by kennel clubs, but it depends entirely on the accuracy of the pedigree. It is valid for 1 generation and it collapses if a parentage is wrong. For a dog that will be used in breeding, we prefer a direct test regardless of what the parents' certificates say. For a pet puppy, clear by parentage from two directly tested parents is perfectly reassuring.

What to ask the breeder, and what should worry you

Ask for the laboratory certificates of both parents, as documents, with the dogs' names, microchip numbers and the laboratory's name legible. A serious breeder sends them without hesitation and often before you ask.

Be wary of any of the following: the phrase "the parents are healthy, they have never had problems", which addresses a different question entirely; certificates you are told you will receive later; a refusal to give the certificates before a deposit; results shown only as a screenshot or a message; and the claim that testing is unnecessary "because our lines have never had it". No line is exempt from a recessive mutation until it is tested.

Beyond the two DNA tests

Genetic testing is the floor, not the ceiling. Serious breeding programmes in this breed also include an annual ophthalmological examination by an ECVO specialist, which detects conditions not covered by DNA tests such as persistent hyperplastic primary vitreous and distichiasis; official hip and elbow scoring, which matters more in this breed than is generally admitted; and a cardiac examination for the heart conditions that occasionally appear in bull breeds.

Increasingly, breathing quality is being assessed as well. The Staffordshire Bull Terrier is not a brachycephalic breed, but the tendency towards ever shorter muzzles in some show lines has consequences, and a dog that struggles in warm weather or after moderate exercise has a welfare problem regardless of how it looks standing still.

The cost of prevention against the cost of the disease

Testing both parents costs around 800 euros in all, once. The lifetime cost of an L2-HGA affected dog runs into thousands, and the cost of cataract surgery for one eye is comparable to the price of the puppy. But the arithmetic is not really the point. The point is that a family who chose a healthy breed and paid for a pedigree puppy should never be put in that position, when a swab and 3 weeks of waiting would have prevented it entirely.

These are not two comparable expenses. Eight hundred euros spent once before a mating sits opposite a monthly cost that lasts as long as the dog does.

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