Mucolipidosis II

Mucolipidosis II is a lysosomal storage disease caused by deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, encoded by the GNPTAB gene. This deficiency prevents proper labeling and transport of lysosomal enzymes. Symptoms include growth retardation, facial dysmorphia and neurological disorders such as ataxia.

Symptoms

The disease progresses rapidly and the life span of affected cats is usually short, usually less than one year. Clinical signs include growth retardation, facial dysmorphia, ataxia and skeletal deformities. In addition, they may experience joint laxity, vertebral fusion and retinal changes resulting in complete blindness.

Disease Management

The management of feline mucolipidosis II focuses on providing supportive care to improve the quality of life of affected cats, as there is currently no cure for this progressive genetic disease.

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

Mucolipidosis II is an inherited lysosomal storage disease characterized by deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase encoded by the GNPTAB gene. This enzyme incorporates a phosphate group to the mannose residues of the hydrolases synthesized in the Golgi apparatus for transport to the lysosomes. Without this modification, the hydrolases cannot properly target the lysosomes to degrade certain compounds, resulting in the accumulation of undegraded oligosaccharides, lipids and glycosaminoglycans within the cells. The causative variant was identified in the Domestic Shorthair cat and consists of a base pair substitution in the GNPTAB gene (c.2644C>T) in exon 13. This mutation introduces a premature stop codon, resulting in the production of a truncated and non-functional protein.

Most affected breeds

Domestic Shorthair

Bibliography

Mazrier H, Van Hoeven M, Wang P, et al. Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease. J Hered. 2003 Sep-Oct