Mucopolysaccharides are complex sulphated sugars with repeating disaccharides that form sulphated glycosaminoglycans (GAG). There are five different types of GAGs: chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, dermatan sulphate, and keratan sulphate. In their synthesis, each GAG is attached to a specific protein core to produce a variety of proteoglycans with many different biological functions. The mucopolysaccharidoses are a group of 11 important lysosomal storage diseases caused by deficient activity of enzymes associated with the lysosomal degradation of one, or sometimes several GAGs.3
Canine Mucopolysaccharidosis I (MPS I) is a condition caused by the deficiency of alpha-L-iduronidase and is most similar to human MPS type I. MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disc degeneration, leading to spinal cord compression and scoliosis.5 Puppies with MPS I appear normal at birth and remain generally healthy for 4-6 months and then show stunted growth, corneal clouding, and progressive, degenerative, noninflammatory joint disease.
Different types have been described in dogs and cats. Type I occurs in Plott hounds and domestic cats. Type VI has been recognized in cats (Siamese) and dogs (Miniature Pinscher and Welsh Corgi). In cats it is caused by a deficiency of arylsulfatase B; in dogs it is the result of excessive dermatan sulfate. Affected animals are small and short and have flattened faces and skeletal abnormalities. Joint laxity caused by abnormalities in ligaments and tendons is also common. Degeneration of intervertebral disks, collapse of disk spaces, vertebral and long-bone osteopenia and spondylosis also develop. Mucopolysaccharide accumulation in the heart valves and arteries can cause rapidly progressing heart failure. Affected dogs remain alert and responsive until their death by natural causes or euthanasia, usually between the ages of 2 and 3 years.
Canine Mucopolysaccharidosis VII is a condition caused by a deficiency of beta-glucuronidase which involves skeletal and joint abnormalities. Progressive noninflammatory bone and joint disease develops. By the age of 3-6 months, affected dogs are unable to stand and the muscles involved in movement waste. Corneal clouding can cause impaired vision, but the impairment is usually less severe than in dogs with MPS I. At the age of 5-22 months, affected dogs often become lethargic and lose interest in their environment. Those signs might be associated with hydrocephalus.
Corneal opacity in a Miniature Poodle diagnosed with mucopolysaccharidosis type VI (source: PubMed)
Diagnosis of mucopolysaccharidosis is made by physical examination, blood tests, and radiographic X-rays of the skeletal system. A special test that detects mucopolysaccharides in the urine (toluidine test) can also be employed. Current treatments for MPS I include hematopoietic stem cell transplantation (HSCT) and enzyme-replacement therapy (ERT), but neither treatment completely ameliorates GAG accumulation or the progression of disease. Early treatment may partially improve these effects [10,11], although cardiac valve disease, corneal clouding and skeletal changes still do not respond well. In MPS I dogs that received HSCT at 5 months of age, radiographic abnormalities were reduced at 20 months but intervertebral space narrowing was still present.4
Pentosan polysulfate (PPS) is a sulfated polysaccharide polymer isolated from beech trees. It has potent anti-inflammatory and weak anti-coagulant activity, and has been marketed in Europe for over 30 years with a very positive safety profile. It is also used in veterinary medicine to treat osteoarthritis. Recently it has been demonstrated that PPS treatment in MPS reduced GAG storage in the MPS dogs. The drug was administered for up to 6 months and no drug-related adverse events were observed.6 Because of the inherited nature of this disease, affected animals should not be bred.
- Dogs By National Research Council Staff, Committee on Dogs, Committee on Dogs National Research Coun, Committee on Dogs, Institute of Laboratory Animal Resources, Commission on Life Sciences, Institute of Laboratory Animal Resources (U.S.), Inc NetLibrary, National Research Council Committee, National Research Council, National Research Council Committee, National Academy of Sciences
- Thomas Carlyle Jones, Ronald Duncan Hunt, Norval W. King. Radiographic Interpretation for the Small Animal Clinician By Jerry M. Owens, Darryl N. Biery
- Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene
- Radiographic Evaluation of Bones and Joints in Mucopolysaccharidosis I and VII Dogs After Neonatal Gene Therapy
- Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs
- Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs. Calogera M. Simonaro, Shunji Tomatsu, Tracy Sikora, Francyne Kubaski, Michael Frohbergh, Johana M. Guevara, Raymond Y. Wang, Moin Vera, Jennifer L. Kang, Lachlan J. Smith, Edward H. Schuchman, and Mark E. Haskins