Mucopolysaccharidosis is a rare autosomal-recessive genetic disease characterized by deficiencies of lysosomal enzymes, leading to accumulation of glycoaminoglycans (GAG) in many tissues resulting in distorted growth or function.
in dogs, three types have been recognised:
- Mucopolysaccharidosis I - deficiency of α-L-iduronidase - Plott Hound, Rottweiler, Boston Terrier
- Mucopolysaccharidosis IIIa - deficiency of N-sulfoglucosamine sulfohydrolase
- Mucopolysaccharidosis VI - deficiency of arylsulfatase B - Huntaway, Miniature Poodle, Miniature Pinscher, Miniature Schnauzer, Chesapeake Bay Retriever, Welsh Corgi
- Mucopolysaccharidosis VII - deficiency of β-glucuronidase ('Sly Syndrome') - Brazilian Terrier, German Shepherd, mixed breeds
Mucopolysaccharides are complex sulphated sugars with repeating disaccharide motifs that form sulphated glycosaminoglycans (GAG). There are five different GAG: chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, dermatan sulphate and keratan sulphate. In this inherited disease, enzyme deficiency of arylsulfatase leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in lysosomes of many different cell types, mainly in the connective tissue.
Affected dogs are usually young (2- 5 months of age), and although showing normal behavioural activities and appetite, are often unable to walk and function properly and have severe growth retardation. Weakness of the hind legs is evident, followed by a progressive dysfunction of all limbs. Neurological disease is not a feature of this condition.
Other typical features include growth retardation, dwarfism, facial and other skeletal dysmorphisms, and corneal clouding. Joints are extremely lax and easily subluxated and radiographic examination showed severe epiphyseal dysplasia. Skeletal disease appears to be more severe in MPS VII compared with MPS I in dogs.
Abnormalities in several other organs are often present including hepatomegaly, tracheal dysplasia, congestive heart failure (due to cardiomegaly, thickening of the heart valves and arterial narrowing due to atherosclerotic ('Hurler') plaques), Wallerian degeneration of the spinal cord, corneal opacities and lymphadenopathy. Ocular lesions are characterized by accumulation of GAG primarily in corneal stromal cells and scleral fibroblasts.
Congenital and progressive signs become evident within the first four weeks of life.
Deficient β-glucuronidase activity leads to an elevation of GAGs in urine and therefore the quantitative measurement of urinary GAGs can be used in screening patients (toluidine test).
Radiographs usually reveal prominent spondyloepiphyseal dysplasia due to a delayed ossification.
Diagnosis is based on DNA testing and demonstration of reduced arylsulphatase B activity (affected dogs usually around 8.0 - 10.0 pmol/min/mg protein (units); normal 1,049 and 1,968 units). Commercial tests are available for diagnosis of MPS VI in Miniature Pinschers and Miniature Schnauzers.
The primary differential diagnosis for this condition would be glycogen storage disease (caused by glucose-6-phosphatase deficiency).
There is no specific treatment for this condition, although enzyme replacement therapy given shortly after birth using recombinant human alpha-l-iduronidase has shown promise in dog studies.
The prognosis is considered poor and many cases are euthanased due to deteriorating quality of life.
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