Mucopolysaccharidosis VII Brazilian Terrier Type (MPS VII)
Mucopolysaccharidosis VII Brazilian Terrier Type (MPS VII) is a hereditary lysosomal storage disorder affecting the Brazilian Terrier dog breed. It is a part of a bigger group of disorders, mucopolysaccharidoses. They are known to affect humans, mice, dogs and cats. 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. 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.
Characteristics and Symptoms
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.
Affected dogs show symptoms already as puppies, around 2 to 5 months of age. They are unable to walk and function properly and exhibit severe growth retardation. Affected puppies usually weight 35% less than their healthy littermates. Hind legs show weakness, which eventually progresses into dysfunction of all limbs. Although severe symptoms, affected puppies show normal behaviour and appetite.
Other typical clinical signs are growth retardation, 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.
Mucopolysaccharidosis VII Brazilian Terrier Type (MPS VII) is caused by a missense mutation of GUSB gene encoding lysosomal enzyme acid hydrolase β-glucuronidase. Determination od the β-glucuronidase acitvity in affected dogs showed that the activity was near absent, only 0.2%, while in carrier dogs it was also reduced.
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.
Hytonen MK, Arumilli M, Lappalainen AK, Kallio H, Snellman M, et al. (2012) A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis VII. PLoS ONE 7(7): e40281. doi:10.1371/journal.pone.0040281
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.