ABSTRACT
Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.
Subject(s)
Disease Models, Animal , Mucolipidoses/genetics , Animals , Cats , Female , Humans , Lysosomal Storage Diseases/genetics , Lysosomal Storage Diseases/metabolism , Lysosomal Storage Diseases/physiopathology , Male , Mucolipidoses/metabolism , Mucolipidoses/physiopathology , Pedigree , Retina/pathology , Time FactorsABSTRACT
A retrospective study of 105 dogs with neurological injury was conducted to evaluate the type and prevalence of complications encountered when treatment consisted of a high-dose corticosteroid protocol. All dogs were treated with high-dose prednisolone sodium succinate (HDPSS) (30 mg/kg body weight, administered intravenously [i.v.] q 6 hrs for 36 hrs). Thirty-five (33.3%) cases developed complications including diarrhea (n = 11), melena (n = 11), vomiting (n = 6), hematochezia (n = 3), hematemesis (n = 1), anorexia (n = 1), or a combination (n = 2). Most complications resolved without additional treatments after termination of the HDPSS therapy. None of the complications were considered serious, and none prolonged hospitalization.