Mucopolysaccharidosis Type VII (Variant 2)

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by deficiency of the enzyme beta-glucuronidase (GUSB). This enzyme is essential for degrading glycosaminoglycans in cell lysosomes. GAG accumulation leads to bone malformations, corneal opacity and neuromuscular dysfunction.

Symptoms

Mucopolysaccharidosis type VII in cats manifests in the first months of life with weakness of the hind legs, paralysis, difficulty walking, and poor growth. Affected cats may have broad faces, ocular opacity, enlarged abdomen, and skeletal deformities. As the disease progresses, they may develop tetraparesis, seizures, and severe joint problems. The condition progresses rapidly and can be lethal within a few months.

Disease Management

Management of MPS VII focuses on alleviating symptoms and improving quality of life, as there is currently no cure for the disease. Management strategies include palliative care such as physical therapy to maintain mobility and prevent joint stiffness.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Mucopolysaccharidosis type VII is a lysosomal storage disease characterized by the accumulation of glycosaminoglycans (GAGs) due to deficiency of the enzyme beta-glucuronidase. The gene affected in MPS VII is GUSB, which encodes this enzyme essential for the degradation of glucuronide-containing GAGs in lysosomes. Beta-glucuronidase is crucial for the recycling of cellular components, and its deficiency causes the accumulation of undegraded GAGs within cells, affecting their normal function and giving rise to the clinical manifestations of the disease. Genetic variants in the GUSB gene have been identified as responsible for MPS VII. In this case, a genetic variant involving two single-base transitions (c.[1423T>G;1426C>T]) in exon 9 of the GUSB gene, affecting adjacent codons, is analyzed. These mutations occur in a highly conserved domain, significantly altering the structure and function of beta-glucuronidase.

Most affected breeds

Not specified

Bibliography

Fyfe JC, Kurzhals RL, Lassaline ME, et al. Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII. Genomics. 1999 Jun 1