Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

DalmatianDalmatian

Hyperuricosuria (Huu)

Related terms: Urate stones, urinary stones - uroliths, urolithiasis, Hyperuricemia

Outline: Many Dalmations have a hereditory abnormality of the mechanism of eliminating waste bodily protein which results in high levels of uric acid in the urine. This causes the formation of solid, hard, urate stones in the kidneys and bladder which can block the drainage of urine causing severe pain and the risk of kidney failure and death.  Through out-crossing with other breeds, Dalmatians have been produced that no longer have this serious genetic fault. 


Summary of Information

(for more information click on the links below)

1. Brief description

Hyperuricosuria is a hereditary defect in the metabolic system for eliminating waste body protein and more specifically of purines within the body. Most dogs break down purines into allantoin, which is a soluble chemical that is excreted in the urine without problems. In Dalmatians, when purines are broken down the waste chemical produced is uric acid instead. This often crystallizes out in the urine and forms urate (bladder) stones. Urate stones that have formed in the urinary system can irritate and inflame the bladder, or, more seriously, block the urinary system leading to rapidly progressive, severe problems and even death due to kidney failure and high blood potassium levels. Blockage of the urinary system leads to a medical emergency, can cause severe pain and malaise, with rapid veterinary treatment being necessary to save life.

2. Intensity of welfare impact    

Hyperuricosuria itself doesn’t cause a problem, but the urate stones that commonly form as a result of it, often do. The intensity of the welfare impact varies depending on where the stones form and where they cause problems. It ranges from moderate, for animals with recurrent bouts of cystitis (inflammation of the bladder), which have moderate pain and discomfort, to severe for individuals with complete blockages. These animals can suffer severe pain and illness and sometimes death. They can be treated but often require major surgery which has its own welfare implications.

3. Duration of welfare impact

Moderately affected Dalamatians, experiencing cystitis, may suffer from this for days to weeks, until adequately treated. Reoccurrences of signs are common in Dalmatians throughout their lives. Blockages of the urinary system can rapidly lead to death within hours if appropriate treatment is not given promptly.

4. Number of animals affected

All Dalmatians are prone to urate stones as all have hyperuricosuria. These stones cause disease more often in males than females. From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are Dalmatians (Lucy Asher 2011, personal communication), we estimate that the UK population size of this breed may be around 60,000.

5. Diagnosis

The presence of urate stones will be suspected by the vet in any Dalmatian having difficulty urinating (dysuria ) or with cystitis (inflammation of the bladder). The signs shown will depend on where the stones occur and whether or not they cause a blockage. Their presence can be confirmed by ultrasound and/or radiography (x-rays). Only analysis of a removed stone can confirm it is made of urate (Dalmatians, like other dogs can get other types of urinary tract stones).

6. Genetics

Hyperuricosuria is inherited as a simple, autosomal, recessive trait. All Dalmatians have the recessive gene and the condition. The gene responsible for hyperuricosuria has been identified as the SLC2A9 gene (Bannasch et al 2008).

7. How do you know if an animal is a carrier or likely to become affected?

All Dalmatians have hyperuricosuria and thus all are prone to develop urate stones. Males are more likely to be affected than females.

8. Methods and prospects for elimination of the problem

As all Dalmatians are affected, it is currently not possible to eliminate this problem from the breed without out breeding to non-affected individuals of a different breed. 


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1. Clinical and pathological effects

Hyperuricosuria (Huu) is a condition in which there are higher than normal levels of uric acid in the urine. Uric acid is a waste product that is produced by the liver as it breaks down purines that are no longer needed by the body or those that have directly come from the diet. Purines are a group of chemicals found in DNA (Deoxyribonucleic acid) and in other molecules important in cellular metabolism, among other places, and thus they are found in all animal and plant cells. Purines are found in higher amounts in high protein foods than low protein foods.

In other breeds of dog,  if the dog has a healthy liver, the uric acid that is formed is further broken down into allantoin which is then excreted from the body via the kidney in the urine and causes no problems. However, in Dalmatians, because of an abnormality in metabolic functioning caused by the inheritance of a faulty gene (VGL  http://www.vgl.ucdavis.edu/services/Hyperuricosuria.php) , most of the uric acid is not broken down, and thus high levels of uric acid appear in the blood and have to be excreted in the urine (Hesse and Neiger 2009) e.g. the uric acid concentration in the urine of normal dogs varies from 10-20 mg/24 hours but in Dalmatians varies between 400-600 mg/24 hours).

These high levels of urinary uric acid predispose Dalmatians to form urate (uric acid salts) stones in their urinary system; usually in the bladder. Most usually ammonium urate stones form (Hesse and Neiger 2009). Other factors can affect both the formation of the stones and whether the stones, once formed, will cause problems. Stones are diagnosed more often in male Dalmatians than females, this is thought to be due to anatomical differences, though the cause is currently unknown (Hesse and Neiger 2009). Also, high protein diets increase the likelihood of stone formation, as does a low water intake and feeding dry, rather than moist, food (Hesse and Neiger 2009).

The signs caused by urate stones in the urinary system can vary from none, with the problem going unrecognised, through to an acute emergency (Hesse and Neiger 2009). This mostly depends on where the stones occur. Sometimes, if they are in the bladder, they may cause no signs at all. At other times they can cause bladder wall irritation and damage leading to inflammation and cystitis resulting in signs such as frequently passing small amounts of bloody urine. Straining to pass the urine frequently occurs. Sometimes bacterial infections occur secondary to the presence of the stone and this is very likely to cause more severe cystitis.

If the stones move and are able to block the urethra (the tube from the bladder to outside) the signs become much worse with the animal showing distress and frequently trying but failing to pass urine. These dogs may vomit, be anorexic (not want to eat) and have a tender abdomen. This is a medical emergency and if an animal is left for long in this state they can rapidly become very sick and even die, due to secondary kidney failure and raised blood potassium levels. Occasionally, the stones form in the urinary system above the bladder and can lead to obstructions in the kidney leading to kidney damage and failure. Or small stones that have formed in the kidney may become stuck in the narrow tubes connecting the kidneys to the bladder (ureters).

Uroliths (stones forming in the urinary system) come in various chemical types, some of which can be dissolved using special diet that for example  make the urine more acidic. Urate stones often need to be surgically removed, though sometimes medical treatment can help dissolve them or prevent them recurring. Medical treatment can often be difficult and is only used in dogs not showing clinical signs (VGL - http://www.vgl.ucdavis.edu/services/Hyperuricosuria.php).

Even after appropriate treatment, urate stones frequently reoccur in Dalmatians. Hesse and Neiger (2009) report that up to 30% of cases recur each year.

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2. Intensity of welfare impact

Inflammation of the bladder (cystitis), due to the presence of urate stones and any secondary bacterial infection, will cause discomfort and often pain on urination. The pain and discomfort can last weeks and these are unlikely to resolve without treatment, which often needs to be surgical. Blockages to urine outflow in the urethra (the tube from the bladder to outside) causes huge distress and pain as the animal repeatedly try to pass urine. The pain increases in intensity as the bladder becomes fuller. Also, due to the associated secondary kidney failure affected individuals rapidly feel very ill, do not want to eat and start to vomit. Animals can die from a blocked urinary system within 24-48 hours without appropriate treatment. Likewise, blockages occurring in kidneys or ureters (the small tubes that carry urine from the kidneys to the bladder) can cause intense pain.

Dogs with bladder stones and clinical signs usually need surgery to remove the stones. Surgical intervention and the invasive procedures necessary for emergency treatment of blockages are stressful to animals and can in themselves cause distress, discomfort and pain.

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3. Duration of welfare impact

All Dalmatians have hyperuricosuria present from birth, are prone to urate stones and these stones can start forming from birth.

The average age for dogs to be diagnosed with urate stones varied between locations and studies. In the USA the average age at diagnosis has been reported as 4.5 years, and in Europe it was 6.3 years (Hesse and Neiger 2009). Of Dalmatians treated for urate stones, 30% will have a reoccurrence within one year. Thus for some affected individuals the likelihood of having recurrent problems with this condition throughout their life is high.

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4. Number of animals affected

All Dalmatians have the genetic mutation which leads to hyperuricosuria and the predisposition for urate stones. 55 to 80% of all urate stones diagnosed in dogs are in Dalmatians according to Hesse and Neiger (2009) and more are in males than females – this is thought to be due to the different anatomy of the male urinary tract. Urate stones are seen commonly in Dalmatians but the actual prevalence within the breed has not been reported. From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are Dalmatians (Lucy Asher, 2011, personal communication), we estimate that the UK population size of this breed may be around 60,000.

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5. Diagnosis

The presence of urate stones will be suspected by the vet in any Dalmatian with the signs of dysuria (difficulty urinating) or cystitis (inflammation of the bladder). The presence of stones can be confirmed by ultrasound and/or radiography (x-rays). Only analysis of a removed stone can confirm it is made of urate (Dalmatians, like other dogs can get other types of bladder and urinary tract stones).

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6. Genetics

Hyperuricosuria is inherited as a simple, autosomal, recessive trait. Individuals have pairs of genes, one of each pair having been derived from each parent. In simple, autosomal, recessive conditions, individuals that have two normal genes or one normal and one mutant gene show no signs of the disease but, in this condition, those individuals with two recessive genes show hyperuricosuria. All Dalmatians have the condition because all have two recessive genes. The normal gene does not exist in the UK Dalmatian populationThe gene responsible for hyperuricosuria has been identified as the SLC2A9 gene (Bannasch et al 2008).

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7. How do you know if an animal is a carrier or likely to become affected?

All Dalmatians have hyperuricosuria and are thus prone to develop urate stones. Males are much more likely to have clinical signs than females. Currently, further advice on which Dalmatians are less likely to develop stones is unavailable, though there are recommendations to try and prevent stone forming in Dalmatians including: feeding a low-purine diet (however, this may predispose Dalmatians to dilated cardiomyopathy leading to heart failure (Freeman et al 1996)), or using a drug called allopurinol to prevent the formation of uric acid (producing xanthine instead) (although this drug does have reported side effects); making the urine more alkaline, with a pH of 7.0; and maintaining a good fluid intake (Hesse and Neiger 2009).

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8. Methods and prospects for elimination of the problem

As all Dalmatians have the gene that causes hyperuricosuria and none have the normal gene it is impossible to eradicate this problem from the breed unless out crossing to other breeds occurs; to introduce the normal gene from another breed. This is currently being tried in California, USA under the name of “The Dalmatian Heritage Project – backcross project” (see http://www.dalmatianheritage.com/about/Seltzer.htm) where out breeding to pointers, carrying the normal gene, is occurring. This will only eradicate the recessive gene if, later in the project, carrier Dalmatian/Pointers are detected and not allowed to breed. This is a complex and difficult task and will take time but there is a test for carrier status identification now available in the USA and UK. (VGL - http://www.vgl.ucdavis.edu/services/Hyperuricosuria.php and AHT -http://www.aht.org.uk/genetics_US.html).

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

AHT (Animal Health Trust) (year unknown) Urate stones – uric acid excretion (Canine Hyperuricosuria). (On-line website) Available at http://www.aht.org.uk/genetics_US.html. Accessed 30.7.10.

Bannasch D, Safra N, Young A, Karmi N, Schaible R and Ling G (2008) Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet, Vol. 4, Issue 11, :e1000246

Freeman L, Michel K, Brown D, Kaplan P, Stamoulis M, Rosenthal S, Keene B and Rush J (2006) Idiopathic dilated cardiomyopathy in Dalmatians: Nine cases (1990-1995). J Am Vet Med Assoc 209: 1592-1596

Hesse A and Neiger R (2009) A colour Handbook of Urinary Stones in Small Animal Medicine. London: Manson Publishing Ltd

VGL (Veterinary Genetic Laboratory) (Year unknown) Canine Hyperuricosuria (On-line website for The School of Veterinary Medicine, Davis, California. Available at: http://www.vgl.ucdavis.edu/services/Hyperuricosuria.php. Accessed on 29.7.10

© UFAW 2011


Credit for main photo above:

By Mark Berbezier (Daisy the Dalmatian) [CC-BY-2.0 (http://creativecommons.org/licenses/by/2.0) or CC-BY-SA-2.0 (http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons