Macular Corneal Dystrophy (MCD) is an inherited eye disease affecting humans and dogs. The disease characterized by progressive diffuse cloudiness of the cornea and the presence of grayish-white spots in the superficial corneal stroma. The disease is caused by a mutation in the CHST6 gene which causes abnormal accumulation of complex carbohydrates called glycosaminoglycans in the cornea, mainly in the keratocytes and the corneal epithelium.

Clinical symptoms are usually seen in affected middle aged dogs, and include: Visual impairment, corneal cloudiness, grey-white spots of various sizes on the cornea, blood vessels maybe seen across the corneal surface, increased intensity of the corneal cloudiness and loss of visual acuity.

This mutation has only been reported in Labrador Retrievers, but may be found in Labrador-cross breeds.

Treatment: in dogs there is no treatment. In human, this is treated by corneal transplant.

Cystinuria is an inherited disorder caused by a defective transport of the amino acid cystine in the kidney tubules. Normally, cystine is filtered in the kidney and reabsorbed within the tubules, resulting in little cystine in the urine. Dogs with Cystinuria do not properly reabsorb the cystine (and a few other amino acids) in the kidney tubules, causing the urine to contain abnormally high levels of cystine. Cystine is insoluble in neutral pH or acidic urine, so excess urinary cystine results in the formation of crystals, which in turn can lead to formation of cystine calculi (stones) in the kidney and/or the bladder. Dogs suffering from Cystinuria suffer repeated urinary tract inflammations, and are at risk for urinary blockage, which can, if not treated promptly, lead to kidney failure, bladder rupture, and death. The average age of onset of clinical signs attributable to Cystinuria is about 4.8 years, but in Newfoundlands, signs appear as early as 6 months to 1 year, suggesting that Newfoundlands suffer from a more severe form of the disorder than other breeds.
Treatment of the Disease
Cystinuria in humans and dogs is generally treated with compounds that bind cystine and prevent crystal formation. The two most common drugs of choice are 2-mercaptopropionylglycine (MPG) and D-penicillamine. Little information is available on effective dosages for Newfoundlands, however, at least one study indicated that affected Newfoundlands require higher dosages of MPG than other dogs with Cystinuria. D-penicillamine was found to be of minimal benefit in reducing cystine calculi. This may relate to the fact that Newfoundlands suffer from a more severe form of the disorder than other breeds. Treatment with MPG can, in some cases, result in dissolution of cystine calculi, therefore eliminating the need for surgical removal of the stones. Unfortunately, some Newfoundlands are poorly responsive to medical treatment, suffering from recurring bouts of urinary dysfunction, and, oftentimes, requiring surgery to resolve urinary calculi.

In male Mastiff, Continental, English, French and Olde English Bulldogs, we test for the marker which has strong association with the occurrence of Cystinuria. Only intact males which are tested homozygous for the marker are known to show symptoms of the disease. Females are not known to show symptoms. Due to high occurrence of the disease it is not recommended to remove carriers from breeding to avoid compromising the gene pool, but carrier should only be bred with clear animals. In affected dogs which are showing symptoms of the disease, castration can alleviate symptoms.

Cystinuria is a well-known hereditary metabolic disorder that leads to the formation of urinary stones and urinary obstruction. It has now been described in over 70 breeds. New studies have shown that this disease is very heterogeneous in terms of inheritance, mutation, frequency, severity, treatment and symptoms. A distinction is now made between the following subtypes of cystinuria affecting the different breeds:

The designation of type I cystinuria is used when the disease shows autosomal recessive inheritance, Type II when inheritance is autosomal dominant, and Type III for sex-limited/androgen-dependent inheritance (PH, UG, unpublished data). Additional types can be assigned if found. Specific mutations within each type should lead to phenotypes that are sufficiently similar that the same medical management and breeding advice applies to all cases within that type. Involvement of the SLC3A1 gene is indicated by adding - A, and similarly addendum of - B indicated involvement of mutations in SLC7A9.

• Newfoundland, Landseer, Labrador: Type I -A - autosomal recessive inheritance
• Miniature Pinscher: Type II - B - autosomal dominant inheritance
• Australian Cattle Dog: Type II - A - dominant inheritance
• Mastiff, Bulldogs, Kromfohrländer and Irish Terrier: Type III - androgen-dependent expression.

The type III genetic test is currently available for the variant which is known to be associated with symptoms of the disease in the Mastiff, Continental, English, French and Olde English Bulldog breeds since December 2016, however, there is currently no test available for Kromfohrländer and Irish Terrier. We test for a marker which is strongly associated with the occurrence of cystinuria. Type III Cystinuria affects only intact male dogs which have two copies of the cystinuria marker (cy/cy). Castration can alleviate the symptoms. Bitches do not show any symptoms but pass on the mutation to offspring.

Prevalence: between 8 and 16% of the dogs are genetically affected, while the carrier rate is between 32 and 50%. Targeted breeding reduces the frequency of the marker associated with the disease and is therefore desirable. Due to the high frequency of the gene, it is advisable that carriers should not taken out of breeding in order maintain the diversity of the gene pool. Dogs (Males or Females) tested Carriers (N/cy) should only be bred with clear dogs (N/N). Bitches tested genetically affected (homozygous for the mutation) (Cy/Cy) should not be removed from breeding but should only be bred with clear dogs (N/N). Mating with free animals is possible without any problems. The Laboklin team will be happy to answer any further questions you may have.

Narcolepsy is a disabling sleep disorder affecting humans and animals. The disease is characterized by daytime sleepiness, cataplexy and striking transitions from wakefulness into REM sleep. A mutation in the gene encoding the receptor for hypocretin (orexin) receptor 2 was identified as the cause for canine narcolepsy.

The genetic defect leading to the disease has been identified. By DNA testing, the responsible mutation can be shown directly. This method provides a very high accuracy test and can be done at any age. It offers the possibility to distinguish not only between affected and clear dogs, but also to identify clinically healthy carriers. This is an essential information for controlling the disease in the breed, as carriers are able to spread the disease in the population, but can not be identified by means of common laboratory diagnostic.

A genetic mutation is respobsible for increased appetite and weight gain in Labrador and Flat-Coated retriever. It is well known that labradors are more motivated by food and are more prone to obesity than other breeds. Researchers at the University of Cambridge found that a deletion in the POMC gene is associated with with Weight, Adiposity, and Food Motivation in Labrador Retrievers, this mutation was also identified in Flat-Coated retrievers and associated with the same symptoms. A DNA test is now available at Laboklin to test for the mutation.

Pyruvate kinase (PK) is an enzyme critical to the anaerobic glycolytic pathway of energy production in the erythrocyte. If erythrocytes are deficient in PK they are unable to sustain normal cell metabolism and hence are destroyed prematurely. This deficiency manifests as an hemolytic anemia of variable severity with a strong regenerative response. In dogs, the anemia is always severe (PCV 10-20%) whereas in cats the anemia shows a regenerative response. Also associated with the disease in dogs but not cats is a progressive myelofibrosis and osteosclerosis of unknown etiology and this feature, along with liver failure, is the major cause of death in affected dogs. The life expectancy of affected dogs is shortened and most die before 4 years of age. PK deficiency has been recognized in both dogs and cats. The dog breeds involved are the Basenji, Beagle, Dachshund, Eskimo, West Highland White Terriers and the Beagle. In cats, PK deficiency has been described in Abyssinian and Somali cats, as well as DSH cats. The feline disease differs from the canine disease in that affected cats can have a normal life span, only intermittently have anemia, and do not seem to develop either osteosclerosis or liver failure. In all breeds the disease is inherited as an autosomal recessive condition. Heterozygotes (carriers) do not have any clinical signs of disease and lead normal lives. They are able to propagate mutations throughout the population however and it is therefore important that carrier animals be detected prior to breeding. PK deficiency can be detected, using molecular genetic testing techniques, in the Basenji, Beagle, Pug, Labrador Retriever, West Highland White and Cairn Terriers and the Beagle. These tests identify both affected and carrier animals. It is also possible to identify animals deficient in PK activity through enzyme analysis in those breeds where a molecular genetic test is not available.

The Kennel Club has agreed a new DNA testing scheme for Hyperuricosuria (HUU) / Urate Stone Disorder (USD) in Dalmatian. Under this scheme, HUU test results can be sent by Laboklin to the Kennel Club to be recorded and published only if the submission and testing procedure complies with the following protocol:

• that dogs to be tested are microchipped and registered before the test sample is taken;
• that the test sample (whether buccal swab or EDTA blood sample or other) is taken by a veterinary surgeon or veterinary nurse who first confirms the microchip identity of the test subject and records both the microchip number and registration name on the sample container/package;
• that the sample is sent directly by the veterinary surgery to LABOKLIN.

  Copies of all future test certificate results issued by LABOKLIN will only be recorded by the Kennel Club at this time provided they comply with the above protocols.

  Please ensure that the veterinary surgeon or veterinary nurse taking the sample complete the vet section on the order form, sign it and stamp it, send it directly to Laboklin and ensure that there stamp is on the package / envelope containing the samples submitted.

Hyperuricosuria is characterized by elevated levels of uric acid in the urine. This disease predisposes dogs to form stones in their bladders or sometimes kidneys. The trait can occur in any breed but is most commonly found in the Dalmatian, Bulldog and Black Russian Terrier. The mutation was recently described in Spanish Waterdog (https://www.ncbi.nlm.nih.gov/pubmed/26538670).

Here at Laboklin we recently tested an Australian Shepherd as carrier of HUU but we have no information about its prevalence in this breed, and therefore testing recomended if your aussie is showing symptoms of the disease.

Myotubular Myopathy is sex-linked inherited muscle disease that occurs in Labrador Retriever and Rottweiler. Symptoms are similar to Centronuclear Myopathy (CNM) / Hereditary Myopathy.

Affected puppies appear normal at birth but they start showing symptoms between 7 and 19 weeks of age. Symptoms include progressive skeletal muscle atrophy, muscle weakness especially in the hind limbs, small stature compared to unaffected littermates, puppies can walk with short choppy strides, collapsing after few strides, difficulty eating due to weakness in mastication muscles, which may lead to dropped jaws, hoarse bark.

The disease progresses rapidly and puppies become unable to stand or raise their heads by 3-4 weeks after the start of the symptoms.

Affected dogs are usually euthanized between 15-26 weeks of age.

Due to the X Linked recessive mode of inheritance, males can either be clear or affected, where as females can be clear, carriers or affected. Females are rarely affected because affected males are usually euthanized at young age. The disease is primarily found in males. Testing enables breeders to identify clear, carrier and affected dogs and help in reducing the occurrence of the disease.

XLMTM is considered rare and we currently have no information about its prevalence in the UK.

Stargardt disease is an inherited retinal degenerative disease that leads to visual impairment and blindness in both human and dogs. Photoreceptors are light-sensing cells found in the retina of the eye. There are two types of photoreceptors: rods and cones. Both rods and cones work together to detect light and convert it into electrical signals, which are then “seen” by the brain. Rods are found in the outer retina and help us see in dim and dark lighting. Cones are found in the macula, which is the part of the retina at the back of the eye and help us see fine visual detail and colour. In Stargardt disease both cones and rods degenerate, but for unclear reasons, cones are more strongly affected in most cases.

Although affected dogs often develop stargard disease symptoms before the age of ten, significant clinical signs appear late in life when affected dogs presenting with noticeable visual impairment around 10 years of age. Dogs that are affected by Stargardt disease don’t usually go completely blind, but retain some degree of vision.

The mutation responsible for Stargardt disease in Labrador retriever has been identified by researchers at The Swedish University of Agricultural Sciences, it is a mutation in the ABCA4 gene and a test is now available at Laboklin. The test will help in breeding healthy dogs.