The following information has kindly been provided by Ron Punter (North of England Irish Terrier Club)

CYSTINURIA IN IRISH TERIERS

Cystinuria is a rare condition -we are appealing for small blood samples (with veterinary reports and pedigrees) from affected Irish Terriers to forward to Dr Prof Leeb's department at University of Berne, Switzerland. 

Research is underway to find a gene variant that is associated with genetic predisposition to the condition and develop a genetic test that can be used by breeders to ensure that no more Irish Terriers are bred that develop the condition.

The Irish Terrier Association (ITA) has funds available to pay owners' veterinary fees for obtaining the samples. If you think you can help please contact the ITA secretary who will give details of exactly what we need.

Notes about the condition 

compiled by Ron Punter

Cystine is a derivative of one of the twenty amino acids that are the building blocks of life - cysteine.

Residual amino acids are usually filtered out and recycled by the kidneys.

When cystine is not being filtered properly it can form into stones (calculi, uroliths) in the kidneys, ureters and bladder. Small stones may pass out of the bladder and through the urinary tract, this can be very painful and there is a high chance of a blockage occurring.

""If there is any change in behaviour or other sign that your dog's urinary tract is blocked or is having trouble urinating, call your veterinarian immediately or go to an emergency clinic if it's after hours, as this is an emergency situation that cannot wait."

Cystinuria is relatively rare and many vets are not aware of it and mistake it for the much more common stones formed from struvites (magnesium ammonium phosphate crystals) caused by a urinary tract infection.

Typically the type of cystinuria that sometimes affects Irish Terriers is late onset about four years old onward.

A nitroprusside test can determine the levels of amino acids in urine - Cystine, Ornithine, Lysine, and Arginine (COLA test) -though it's only cystine that causes a problem. Fairly obviously, high COLA levels mean the dog is at risk of Cystinuria.

Dietary changes and drug therapy have little effect in type3 but castration seems to be a complete cure (assuming stones have been removed) and COLA levels return to normal.

Cystinuria in humans is a genetic recessive trait and it is often misquoted as being the same in dogs but in fact there are several different defective genes which are now put into three divisions- in some breeds it is indeed recessive- designated type1 but in some others it's dominant -designated type2. In Irish Terriers (and Scottish Deerhounds) the condition only occurs in male dogs that have not been neutered - designated type3, this is thought to be testosterone (male hormone) dependent and genetically autosomal (not on X chromosome in the way that sex linked conditions often are.) It is not yet known if the mode of inheritance is dominant or recessive.

References: 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946761/
SLC3A1 and SLC7A9 Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System
A.-K. Brons,† P. S. Henthorn,† K. Raj,† C. A. Fitzgerald,† J. Liu,† A. C. Sewell,§ and U. Giger†

https://sdcahealth.wordpress.com/health-issues/cystinuria/
Scottish Deerhound Club of America -Cystinuria 

HYPERKERATOSIS REPORT

As we all know, the Irish Terrier basically is a sound and healthy breed inspite of its small population and rather narrow genetic pool. The main health issue that we have been dealing with over recent years is Digital Hyperkeratosis (CF) now termed Hereditary Footpad Hyperkeratosis (HFH). “It’s always been in the breed”, the breeders used to say in the old days, shrugging their shoulders. But modern researchers being convinced that a disease of genetic origin must not be accepted as a sword of Damocles, as fate decided to find out the way of inheritance in order to keep the breed healthy and to help to make it even healthier again. The CF-riddle has been solved quite recently by Prof. Dr. Tosso Leeb (University of Bern, Switzerland).The marker gene has been identified!

Designated ‘HFH-A’ the recessive marker gene is a variant of the FAM83G gene. The condition is usually first seen by owners at 4–5 months of age and involves all footpads. With time horny protrusions appear on the rims of the footpads and the pad surface becomes hard and develops cracks. Affected animals avoid walking on irregular surfaces and may go lame. The nails of affected dogs are very hard and seem to grow faster. Visual diagnosis is not always simple as the intensity of clinical symptoms can vary between animals or even between pads on the same animal therefore the DNA test is the conclusive diagnosis. Inspections should be careful not to mistake for HFH accidental cuts or splits or abrasions, such as those from exercise on hard surfaces.

The results of the research were published in spring 2014 and the genetic test became available after evaluating its reliability and technical feasibility. This is a wonderful contribution for all health concerned breeders as the test now allows us to find out about the genetic disposition of our breeding stock and especially about potential carriers, those dogs which are so risky in breeding as they do not show any signs of the disease but, if bred to a carrier partner, may produce affected offspring. Swiss researcher, Prof. Dr.Tosso Leeb, having managed to find the gene marker in the Kromfohrländer breed, directly went on with his research on the Irish Terrier. He had been given samples of dogs from many years ago and these were the base for his studies together with samples he had asked from dogs of a Swiss breeder and also was given samples from dogs in Germany and Switzerland affiliated with her stock. In this context it should be mentioned that in Switzerland already some years before Dr. Claude Schelling from ETH Zurich had begun CF-research but had not been given the funding to complete the study.

In 2008 the French group (Antagène and Rennes University) started on a different background: after having identified the gene marker for a similar condition in the Dogue de Bordeaux, Dr. Anne Thomas was interested in doing the same research for the Irish Terrier breed and attended a show in Lyon with the aim of collecting samples from those Irish Terriers shown at that particular show. There she met the French breeder Frédérique Andersson who immediately agreed collecting samples all over France. Due to personal relations this idea spread to Germany where Andrea Gasch and Helga Richter-Lönnecke were asked by Antagène to collect samples and then spread to Britain where Susan Seabridge spent a tremendous amount of time and energy in collecting samples and biopsies. In Latvia it was Tatjana Necajeva who as well as in her country helped find in Russia several affected dogs based on well- known Western European lines. The French research therefore focused exclusively on contemporary dogs. Early November 2013, Anne Thomas presented the Antagène work at the German breeders’ annual reunion informing them that they had not yet reached a conclusion. At this time neither Leeb nor Thomas knew that both scientist groups were working on the same subject which Prof. Dr. Leeb was able to report the successful conclusion and, being advised of their interest, invited the Antagène group to collaborate with him for the final evaluation.

Antagene were able to carry this work forward and offer testing to identify those Irish Terriers that are designated: 'Affected'; 'Carriers'; or 'Clear' of HFH. Their services can be found on http://www.antagene.com. There are no restrictions on testing based on Prof Leeb's research. The UK Laboratory, Animal DNA Diagnostics offers testing from simple at home cheek swabs (including puppies) and have collected samples from UK dogs of known status in order to validate their testing. Details are available on https://www.animaldnadiagnostics.co.uk .

Now that the genetic status of dogs can be identified correctly, all dogs can be retained for breeding if they are desirable breeding stock. Mating combinations can be decided which avoid the risk of producing Foot Hyperkeratosis affected pups. The different breeding combinations and their outcomes are listed below. The combinations in red risk affected pups and should be avoided, but there are recommended combinations which include both carriers and indeed affected dogs (in fact the affected – clear combination has the advantage that the resulting pups do not need to be genetically tested as they will all be carriers). Breeding from an affected dog could therefore be contemplated if he was a exceptional dog in other ways. Obviously the LONG TERM aim is to gradually remove the carriers from the breeding group, but this does diminish the gene pool, so in an ideal world would be undertaken very gradually. Unfortunately, often breeders are too eager to discard carriers from breeding!

The following table which makes it easier to understand has been provided by Dr June Swinburne, Animal DNA Diagnostics.

Affected x Affected = 100% Affected

Affected x Carrier = 50% Affected/50% Carrier

Affected x Clear = 100% Carrier

Carrier x Carrier = 25% Affected, 25%Clear, 50% Carrier

Carrier x Clear = 50% Carrier, 50% Clear

Clear x Clear = 100% Clear