Mucopolysaccharidosis Type I

Mucopolysaccharidosis type I (MPS I) is a genetic disease due to deficiency of the enzyme alpha-L-iduronidase, crucial for degrading glycosaminoglycans in lysosomes. This causes accumulation of these compounds in various tissues, manifesting with bone deformities, distinctive facial features, neurological and ocular problems.

Symptoms

Affected cats show clinical signs including bone and joint deformities such as hip subluxation and broad cervical vertebrae. In addition, they have distinctive physical features such as a flat, broad face, large head, small ears and thick skin on the neck. Other common symptoms include abnormal gait, corneal clouding, cognitive impairment and heart disease, often manifested as a heart murmur.

Disease Management

Treatment of MPS I is based on symptomatic and supportive management strategies, since curative treatment is not yet available. Enzyme replacement therapy, involving administration of recombinant alpha-L-iduronidase enzyme, may be considered, although its efficacy and availability may vary. In addition, gene therapies using adeno-associated virus (AAV) vectors, such as AAV9, are being investigated. However, both of these treatments are still in the developmental stage.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Mucopolysaccharidosis type I or Hurler syndrome is a genetic disease caused by deficiency of the enzyme alpha-L-iduronidase (IDUA), a lysosomal hydrolase crucial for the degradation of iduronic acid residues in the glycosaminoglycans dermatan sulfate and heparan sulfate. In cats, causative variants of mucopolysaccharidosis type I have been identified, such as a 3 base pair deletion in the first intron of the gene encoding IDUA, preventing proper excision of the intron and leading to the MPS I phenotype. This specific mutation predicts the deletion of an aspartic acid residue thus affecting IDUA enzymatic activity and protein expression.

Most affected breeds

Domestic Shorthair

Bibliography

He X, Li CM, Simonaro CM, et al. Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats. Mol Genet Metab. 1999 Jun