Mucopolysaccharidosis VII in a Cat Caused by 2 Adjacent Missense Mutations in the GUSB Gene.

BACKGROUND: Mucopolysaccharidoses (MPS) are common lysosomal storage disorders causing typically progressive skeletal and ocular abnormalities. OBJECTIVES: To describe the clinic features, metabolic profile and a unique mutation in a domestic shorthair (DSH) kitten with MPS VII. ANIMALS: Affected kitten and 80 healthy cats. METHODS: Serum lysosomal enzyme activities and urinary glycosaminoglycan (GAG) accumulation were assessed. Exons of the ß-glucuronidase gene (GUSB) were sequenced from genomic DNA and genotyping was conducted. RESULTS: A 3-month-old DSH cat was presented for stunted growth, paresis, facial dysmorphia, multiple skeletal deformities, and corneal opacities. Evaluation of blood smears disclosed metachromatic granules in leukocytes and a urinary mucopolysaccharide spot test was positive. The proband had no GUSB activity but normal or increased activities for other lysosomal enzymes. Sequencing of the GUSB gene from the proband and comparison to the sequence of 2 healthy cats and the published feline genome sequence demonstrated 2 unique single base transitions (c.1421T>G and c.1424C>T) in exon 9, altering 2 adjacent codons (p.Ser475Ala and p.Arg476Trp). These amino acid changes are in a highly conserved domain of the GUSB protein and nontolerable to maintain function. Moreover, the p.Arg476Trp mutation previously has been identified in human patients. None of the other clinically healthy cats had these mutations. CONCLUSIONS AND CLINIC IMPORTANCE: The diagnostic approach to MPS disorders is delineated. This is only the second mutation known to cause MPS VII in cats. Similarly, 2 different mutations have been described in MPS VII dogs, thereby showing the molecular heterogeneity of MPS VII in companion animals.

Prevalence of mucopolysaccharidosis type VI mutations in Siamese cats.

Mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease, is one of the more prevalent inherited diseases in cats and is commonly found in cats with Siamese ancestry. The prevalence of 2 known MPS VI mutations in cats was investigated in 101 clinically normal Siamese cats, in 2 cats with clinical signs of MPS VI, and in 202 cats from 4 research colonies. The mutation L476P which causes a severe clinical phenotype, was present on both alleles in the known MPS VI cats from Italy and North America and was present in all research colonies that originated from North America. However, LA76P was not detected in the Siamese population screened. In contrast, the mutation D520N, which causes a mild clinical phenotype, was identified in 23 of 202 (11.4%) alleles tested in Siamese cats from 3 continents, 2 of which were homozygous for D520N. Thus, the D520N mutation was widespread, and it is likely that cats inheriting both mutations (LA76P/D520N compound heterozygotes) would be in the general Siamese population, particularly in North America. Practitioners should note the high incidence of degenerative joint disease in these animals.

Lipid composition and biosynthesis in the gingiva of the domestic cat.

Periodontal disease in the domestic cat may assume debilitating and serious consequences; however, little is known of the biochemical composition or metabolism of feline gingiva in health or disease. In this report the chemical composition and metabolism of gingival lipids from inflamed an non-inflamed sites is presented and compared to other species with naturally occurring periodontitis. The neutral and phospholipid composition of feline gingiva was found to be distinct from that of porcine and human. As a measure of de novo lipid synthesis, the total incorporation of 14C-acetate into fractionated lipid components was determined and revealed an approximate 2 to 3 fold decrease in inflamed versus non-inflamed gingiva. The decrease in 14C-acetate incorporation appeared to result from a 2-fold increase in free acetate pools in inflamed compared to non-inflamed gingival samples, since total lipase and phospholipase activity were comparable in inflamed and non-inflamed gingiva and total lipid composition was not changed between inflamed and non-inflamed sites. These data are similar to those reported for periodontally involved human gingival tissue and suggest a common effect of periodontal inflammation on lipid metabolism in both species.