Mucopolysaccharidosis VI or mucolipidosis is a variant form of mucopolysaccharidosis caused by a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase).

Deficiency in G1cNAc-phosphotransferase leads to decreased enzyme activity, resulting in incomplete degradation of the glycosaminoglycan (GAG) dermatan sulfate, and accumulation of breakdown products in cells and tissues. These breakdown products contribute to lysosome damage, cell death, and organ dysfunction.

MPS VI has been reported in Siamese, Tonkinese, Balinese and Domestic shorthair cats and considered homologous to I-cell disease (or mucolipidosis III) in humans. This disorder is also known as the Maroteaux-Lamy syndrome. It has been separated into two subgroups, severe and mild forms, based on clinical manifestations. Both are characterized by growth retardation, hypertelorism, corneal clouding, a depressed nasal bridge, hepatosplenomegaly, and normal or near-normal intelligence. Cardiac valvular disease similar to that of MPS I also occurs. Hydrocephalus and atlantoaxial subluxation, consequent to hypoplasia of the odontoid process, are frequent complications.

Radiographically, the disease is characterized by severe dyostosis multiplex. Prominent lesions include localized constriction of metaphyses, irregular epiphyseal ossification, paddle- shaped ribs , a hypoplastic odontoid process, hypoplastic cervical vertebrae, and a shoe-shaped sella turcica. Alder-Reilly bodies are present in the majority of leukocytes. Arylsulfatase B is deficient in all tissues, and partially degraded dermatan sulfate is excreted in excess in the urine. Mildly affected patients are often not diagnosed until adulthood, when decreased joint mobility becomes a problem^[1].

Clinical signs

Mucopolysaccharidosis type VI is characterized by organomegaly, corneal clouding, and skeletal dysplasia. Affected cats appear dull, ataxic, and may have decreased muscle tone. Radiographic abnormalities are seen as early as 2 weeks of age and lesions include long bone metaphyseal flaring, radial bowing, and antebrachial-carpal joint luxation. Fusion of cervical and lumbar vertebral bodies develop within the first 5 months of life. In some severely affected cats, spina bifida and hemivertebra have been noted. Retinal degeneration may be detected around 2 – 3 months of age^[2].

Diagnosis

The condition has an autosomal recessive mode of inheritance and affected cats either die or require euthanasia within 1 day to 7 months of age. The urine mucopolysaccharide spot test is negative. The enzyme GlcNAc-phosphotransferase is deficient in leukocytes and cultured fibroblasts. Inclusion bodies have been detected in cultured fibroblasts but not in white blood cells. Inclusions have also been seen in endothelial cells and chondrocytes. Storage lysosomes contained oligosaccharides, mucopolysaccharides, and lipids. Tissues most affected are bones, cartilage, skin, and other connective tissues. Parenchymal cells of liver and kidney are unaffected, as is skeletal muscle. Few cerebral cortical neurons show lipid inclusions and peripheral nerves appear normal. It should be noted that the subtle neurologic signs in affected cats are believed to be secondary to the orthopedic changes.

Treatment

Selective treatment using enzyme replacement therapy (recombinant human N-acetylgalactosamine-4-sulfatase (rh4S)) have shown some improvement when given as a low-dose (1 mg/kg) long-term protocol parenterally or intra-articularly^[3]

References

1. ↑ Cowell KR, Jezyk PF, Haskins ME et al (1976) Mucopolysaccharidosis in a cat. J Am Vet Med Assoc 169:334
2. ↑ Jezyk PF et al (1977) Mucopolysaccharidosis in a cat with arylsulfatase-B deficiency: A model of Maroteaux-Lamy syndrome. Science 198:834
3. ↑ Crawley, A et al (2004) Monitoring dose response of enzyme replacement therapy in feline mucopolysaccharidosis type VI by tandem mass spectrometry. Ped Res 55(4):585-591