Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene

Abstract

AIM: To investigate and characterise an inborn error of metabolism in a dog with skeletal and ocular abnormalities.

METHODS: A 2.5-year-old small male Miniature Poodle-like dog was presented with gross joint laxity and bilateral corneal opacities. Clinical examination was augmented by routine haematology, serum chemistry, radiographs, pathology, enzymology and molecular genetic studies. Euthanasia was requested when the dog was 3 years of age because of progressively decreasing quality of life.

RESULTS: Radiology revealed generalised epiphyseal dysplasia, malformed vertebral bodies, luxation/subluxation of appendicular and lumbosacral joints with hypoplasia of the odontoid process and hyoid apparatus. These clinical and radiographic findings, together with a positive urinary Berry spot test for mucopolysaccharides, and metachromatic granules in leucocytes, were indicative of a mucopolysaccharidosis (MPS), a lysosomal storage disease. Histological lesions included vacuolation of stromal cells of the cornea, fibroblasts, chondrocytes, macrophages and renal cells. The brain was essentially normal except for moderate secondary Wallerian-type degeneration in motor and sensory tracts of the hind brain. Dermatan sulphate-uria was present and enzymology revealed negligible activity of N-acetylgalactosamine-4-sulphatase, also known as arylsulphatase B, in cultured fibroblasts and liver tissue. A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme's gene was identified (c.103_124del), which caused aframe-shift and subsequent premature stop codon. The “Wisdom pure breed-mixed breed” test reported the dog as a cross between a Miniature and Toy Poodle.

CONCLUSIONS: The clinicopathological features are similar to those of MPS type VI as previously described in dogs, cats and other species, and this clinical diagnosis was confirmed by enzymology and molecular genetic studies. This is an autosomal recessively inherited lysosomal storage disease.

CLINICAL RELEVANCE: The prevalence of MPS VI in Miniature or Toy Poodles in New Zealand and elsewhere is currently unknown. Due to the congenital nature of the disorder, malformed pups may be subject to euthanasia without investigation and the potential genetic problem in the breed may not be fully recognised. The establishment of a molecular genetic test now permits screening for this mutation as a basis to an informed breeding policy.

Key Words:

• Lysosomal storage disease
• mucopolysaccharidosis
• Arylsulphatase B
• Miniature/Toy Poodle
• mutation

Acknowledgements

The authors would like to acknowledge Professor Keith Thompson (IVABS) for Figure 1, Dr. Jianyu Chen (Manawatu Microscopy and Imaging Centre, Massey University, Palmerston North, New Zealand) for preparation of epoxy resin sections, Mrs E. Luxton (IVABS, Massey University) for preparation of the paraffin sections and Mrs Gloria Owens, (Metabolic Laboratory, Genetics and Molecular Pathology, SA Pathology, Adelaide) for the glycosaminoglycan analysis of urine. We thank them for their contributions to this investigation. The molecular genetic investigation was supported by a grant from the National Institutes of Health (NIH-RR02512).

Notes

*Non-peer-reviewed

Additional information

Notes on contributors

DJ Thompson

¥Current address: Perth Veterinary Specialists, Veterinary Imaging Centre, 305 Selby St. North, Osborne Park, WA 6017, Australia.