In other species: dog , taurine cattle

Categories: Lysosomal storage disease

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607014 (trait) , 607015 (trait) , 607016 (trait) , 252800 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 1999

Cross-species summary: Also known as Hurler syndrome

Species-specific description: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease characterized by intracellular accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfates. Affected cats have flat, broad faces, large heads, small ears, thick skin over the dorsal neck, wide cervical vertebrae, and hip subluxation. Other signs include abnormal gait, corneal clouding and some have a cardiac murmur of mitral insufficiency. The mode of inheritance is autosomal recessive, and the causative mutation is a 3 base-pair deletion in the IUDA gene. Affected cats are deficient in the lysosomal enzyme alpha-L-iduronidase, which is a part of the breakdown pathway of glycosaminoglycans. Since affected cats cannot adequately break down the GAGs, they accumulate in multiple cell types and cause clinical signs. There is a test available to detect the mutation. Siblings of affected cats should be tested. Breeding of affected or carrier cats should be avoided. Edited by Mark Haskins, VMD, PhD

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), He et al. (1999) showed that the causative mutation is a 3 bp deletion in the IDUA gene, which results in removal of an aspartate residue from the finished polypeptide.

Clinical features: Affected cats have flat, broad faces, large heads, small ears, thick skin over the dorsal neck, wide cervical vertebrae, and hip subluxation. Other signs include abnormal gait, corneal clouding and some have a cardiac murmur of mitral insufficiency. Fine metachromatic granules occur in lymphocytes. GAGs are detectable in urine by a simple alcian-blue spot test (Haskins et al., 1979, Haskins et al., 1983).

Pathology: Affected cats are deficient in the lysosomal enzyme alpha-L-iduronidase, which is a part of the breakdown pathway of glycosaminoglycans. It is a hydrolase that removes iduronic acid residues from dermatan sulfate and heparan sulfate. Since affected cats cannot adequately break down the GAGs, they accumulate in multiple cell types and cause clinical signs (He et al., 1999). Thickened cardiac valves and cordae tendinae, and cerebral ventricle dilatation are observable on necropsy, along with a wide cervical spine (Haskins et al., 1979). Membrane-bound cytoplasmic inclusions aggregate in hepatocytes, Kupffer cells, fibroblasts, cartilage, cornea, retinal pigment epithelial cells, neurons, and white blood cells. These cells can appear to have vacuolated cytoplasm on histologic examination (Haskins et al., 1979). On examination by electron microscopy, brain and spinal cord neurons contain membrane-bound “zebra bodies” (He et al., 1999).

Prevalence: Southeastern Pennsylvania

Control: Siblings of affected cats should be tested. Breeding of affected or carrier cats should be avoided.

Genetic testing: There is a test available to detect the mutation.

Breed: Domestic Shorthair.
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: