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.