The diagnosis, control and treatment of hereditary diseases play an important role in modern veterinary medicine. The Section of Medical Genetics at University of Pennsylvania has been involved in the discovery of hereditary disorders of companion animals for several decades. A particular area of research has been the study of lysosomal storage diseases (LSD) including Mucopolysaccharidosis (MPS). Several MPS disorders have been identified and the disease processes have been characterized. Furthermore, some disease-causing mutations have been identified and breed-specific DNA tests have been established for the diagnosis of affected animals and carrier detection. (Supported by National Institutes of Health, the National MPS Society, Inc., and the Canine Health Foundation.)

MPS, a group of inherited metabolic disorders, is due to defects in a series of catabolic enzymes, which results in multisystemic accumulation of improperly degraded glycosaminoglycans (GAGs). The undegraded GAGs usually leak out of the cells and can be detected in the urine, which serves as a screening test. The common clinical signs include growth retardation, skeletal deformities, corneal cloudiness, facial dysmorphia and, in some cases, neurological signs. MPS disorders have been identified in both dogs and cats (see Table).

The first canine MPS disorder identified was MPS VII in a mixed breed dog at the University of Pennsylvania about 25 years ago. The study of this and other MPS disorders led to better understanding of the clinic pathologic process and also to the first successful attempt to treating a multisystemic disorder with gene therapy. The same mutation causing MPS VII in the original mixed breed dog has now been identified to cause MPS VII in German Shepherds; two separate families have recently been found in Georgia and Minnesota. We have also documented MPS VII in a Rat Terrier. MPS I, which was first recognized in the Plott Hound, has since also been identified in a Rottweiler. All MPS disorders are autosomal recessively inherited, except for MPS II reported in a Labrador Retriever, which is inherited as an x-linked trait. MPS III, also known as Sanfilippo syndrome, is unique in that this is the only MPS disorder with mostly neurologic signs such as ataxia and tremors. MPS IIIA occurs in Wirehaired Dachshunds and the New Zealand Huntaway dog. MPS IIIB has been found in Schipperkes (and also emus). Typically dogs with MPS IIIB do not exhibit clinical signs until they are two years of age and their condition is slowly progressive until they need to be euthanized before 5 years of age. The disease-causing mutation has been identified, and the results from screening >1000 Schipperkes would indicate that the mutant allele seems to be very prevalent in the breed (almost 20% of a somewhat biased sample were carriers). MPS VI was first seen in Miniature Pinschers with stunted growth and skeletal abnormalities mostly involving the hips, hence they were misdiagnosed as having hip dysplasia or femoral head necrosis. The molecular defect in this breed has been identified and screening of Miniature Pinschers for carriers and affected dogs is now possible. Further studies are in progress to define the MPS VI mutation in affected Chesapeake Bay Retrievers and Miniature Schnauzers. MPS I, MPS VI, and MPS VII have also been observed in cats. In addition, mucolipidosis II, a unique and devastating storage disease, which is closely related to MPS, has recently been characterized in domestic shorthair cats from the clinical signs to the molecular defect.

MPS may be suspected based on clinical signs, white blood cell granules, and a positive urine MPS spot test. Further diagnostics includes dramatically reduced specific catabolic enzyme activity, and molecular analysis. While enzyme testing requires special handling of fresh blood samples with a control sample to be shipped on ice overnight, samples for DNA testing are stable and can be performed on small EDTA blood sample or cheek swab shipped by regular mail. For further information, contact the Josephine Deubler Genetic Disease Testing Laboratory at the University of Pennsylvania http://www.vet.upenn.edu/penngen, email at penngen@mail.vet.upenn.edu or fax at 215-573-2162.

Mucopolysaccharidoses and other Lysosomal Storage Diseases in Animals