Mucopolysaccharidosis VII Shepherd Type (MPS VII)
Mucopolysaccharidosis VII Shepherd Type (MPS VII) is a hereditary lysosomal storage disorder affecting Shepherd breeds, such as Belgian Shepherd Dog, German Shepherd Dog, White Swiss Shepherd Dog. It is a part of a bigger group of disorders, mucopolysaccharidoses. Until now, eleven types of mucopolysaccharidosis have been differentiated in humans. They vary in clinical symptoms, but some characteristics are common to all forms, such as dwarfism, undeveloped epiphyseal centers, dysostosis multiplex, facial dysmorphia, corneal clouding and organomegaly. They are known to affect humans, mice, dogs and cats. Mucopolysaccharidosis type VII was first time reported in a mix breed dog in the 1990’s. It is also known as the ‘Sly syndrome’.
The extracellular matrix (ECM) is the main component of bone and other connective tissues. It consists mainly of collagen and proteoglycans. Several skeletal disorders have been associated with mutations in genes associated to structural proteins of the extracellular matrix.
Symptoms and Characteristics
Skeletal deformities are also characteristically symptom of lysosomal storage disorders, mucopolysaccharidoses. These disorders, lysosomal enzymes, acid hydrolase β-glucuronidase, are dysfunctional, which results in accumulation of glycosaminoglycans (GAG) in lysosomes. GAG accumulation is happening in lysosomes in different cell types, but mainly in the connective tissues.
First symptoms appear between 4 to 8 weeks of age. Affected puppies are unable to walk and function properly. Severe growth retardation is recognized, where affected puppies usually weight 35% less than their healthy littermates. In hind legs weakness is present, which eventually progresses into dysfunction of all limbs. Head appears as disproportionally large with short muzzle, broad face, low set ears and domed skull. Eyes seems cloudy and smaller than from the healthy littermates. No behavioral changes or changes in appetite have been observed in affected puppies.
Except growth retardation, other typical clinical signs are dwarfism, facial and also other skeletal dysmorphisms, such as epiphyseal dysplasia of the vertebra and long bones, and corneal clouding. Joints are extremely loose and easily subluxated. Cardiac abnormalities have been reported as well.
Due to poor quality of life, affected dogs are usten euthanized.
Mucopolysaccharidosis VII Shepherd Type (MPS VII) is caused by a missense mutation of GUSB gene encoding lysosomal enzyme acid hydrolase β-glucuronidase.
The disorder is inherited as an autosomal recessive trait. Healthy parents of an affected dog are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Haskins ME, Aguirre GD, Jezyk PF, Schuchman EH, Desnick RJ, Patterson DF. Mucopolysaccharidosis type VII (Sly Syndrome). Beta-glucuronidase-deficient mucopolysaccharidosis in the dog. Am J Pathol. 1991 Jun;138(6):1553-5.
Ray J, Bouvet A, DeSanto C, Fyfe JC, Xu D, Wolfe JH, Aguirre GD, Patterson DF, Haskins ME, Henthorn PS. Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. Genomics. 1998 Mar 1; 48(2):248-53.