Mucopolysaccharidosis (MPS) – a condition in which long chain sugars of the body are not properly broken down.  Cellular accumulation is systemic and can result to varying degrees in skeletal deformities, including defects in the sternum, vertebrae, and joints, corneal cloudiness, facial dysmorphia, and neurological signs.  The skeletal malformations are generally recognized within the first few days to months of life, whereas the neurological signs do not appear until adulthood in some forms of MPS.  A definitive diagnosis is reached by demonstrating deficient activity of a specific enzyme in blood or tissue, or by DNA testing, if the disease-causing mutation in a breed has been documented.   

There are 7 types of MPS, labeled as MPS I thru VII.  All are autosomal recessive except MPS II, which is an x-linked recessive.  Each type displays itself differently. 

DNA tests for MPS disorders require cheek swabs or an EDTA blood sample and are being offered through the Josephine Deubler Genetic Disease Testing Lab at the University of Pennsylvania.  DNA can be acquired from frozen semen as well. 

(http://www.vet.upenn.edu/research/centers/penngen/services/)

As in any autosomal recessive disease, if parents are clear, offspring do not need tested, as they will also be clear.  The test will be offered at an introductory rate of $50 and then will be set at a standard rate of $75 once established.  The subject only needs tested once in its lifetime.  Urine metabolic screening can be used to spot test for puppies.

In humans, each MPS disorder occurs relatively rarely but all together represent a large important group (1 in 5,000 births).  Some MPS disorders have been described in several animal species including cats, mice, goats, and emu, and several have been identified in different canine breeds. 

MPS I – First recognized in the Plott Hound, and has since also been identified as an isolated case in a Rottweiler.

MPS II – Seen in Labrador Retrievers (this is the x-linked recessive trait).

MPS III – Also known as Sanfilippo syndrome; unique in that it is the only one with neurological signs such as ataxia and tremors.  Occurs in Wirehaired Dachshunds and the New Zealand Huntaway dog; most recently found in Schipperkes, which do not exhibit clinical signs until 2 years of age.  The disease is slowly progressing resulting in the need for euthanasia by 5 years of age.  They have now identified the mutation in Schipperkes and from screening 1,000 of them, they have found that the mutant allele is very prevalent in that breed.

MPS VI – First seen in the Miniature Pinscher with stunted growth and skeletal abnormalities mostly involving the hips, and were therefore misdiagnosed with hip dysplasia or femoral head necrosis.  The molecular defect in this breed has just 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 Chesapeake Bay Retrievers and Miniature Schnauzers (these breeds do not have the same mutation as found in the Miniature Pinscher).

MPS VII – The first canine MPS disorder identified was in a mixed breed dog at the University of Pennsylvania 25 years ago.  The same mutation causing MPS VII in the original mixed breed dog has now been identified to cause MPS VII in the German Shepherd Dog.

Researchers are also interested in determining if the common occurrence of Legge-Calves-Perthes (LCP) disease in Miniature Pinschers and other small breeds is related to MPS disorders.  LCP is a devastating hip disease with necrosis of the femoral head due to an unknown cause.  Although LCP is different from hip dysplasia and MPS, similar bone changes are observed and, therefore, MPS and LCP disease may be related in these breeds. 

AWS Partners’ recommended resources:

University of Pennsylvania Veterinary Medicine, Department of Clinical Studies – Philadelphia (Section of Medical Genetics)

http://www.vet.upenn.edu/research/centers/penngen/

Therapeutic Neonatal Hepatic Gene Therapy in Mucopolysaccharidosis VII Dogs

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232044&dopt=Abstract

Therapeutic Neonatal Hepatic Gene Therapy in Mucopolysaccharidosis VII

http://www.pnas.org/cgi/reprint/99/20/13102.pdf

Canine Mucopolysaccharidosis Type IIIB: Sanfilippo Type B Syndrome Identified in Schipperke Dogs

http://www.arc.ucla.edu/biolchem/mps/01therapy/abstracts/EllinwoodNM.htm

Mutation Causing a Storage Disease in Miniature Pinschers Identified

http://www.minpin.org/research.html