Alpha mannosidosis is an autosomal recessive lysosomal disease caused by deficiency of the enzyme alpha mannosidase, encoded by the MAN2B1 gene. This enzyme is crucial for the degradation of mannose-rich oligosaccharides within lysosomes. In its absence, these oligosaccharides accumulate in body cells, especially in the central nervous system, bones, and sensory organs such as the eyes and ears.
Symptoms
Alpha-mannosidosis presents with a number of severe clinical signs that impact multiple body systems. Affected cats show severe neurological deficits, such as tremors, loss of balance, nystagmus and hearing loss. They also experience liver enlargement (hepatomegaly), hydrocephalus, skeletal deformities, growth retardation, enlarged gums, and corneal and lens opacities. Without treatment, the lifespan of these cats is reduced to approximately six months.
Disease Management
The management of feline alpha-mannosidosis focuses on therapies that can alleviate symptoms and prolong the lives of affected cats. Gene therapy using an AAV1 viral vector and hematopoietic stem cell transplantation are promising approaches.
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, even if they do not show symptoms, is not recommended.
Technical report
Alpha mannosidosis is a lysosomal disease where mannose-rich oligosaccharides accumulate due to deficiency of the enzyme alpha mannosidase, essential for breaking down these compounds in lysosomes. This enzyme is crucial in the metabolism of glycoproteins in various cells, including neurons and immune cells. The causative mutation, a 4-base pair deletion (c.1749_1752del) in the MAN2B1 gene, is specific to Persian cats with alpha-mannosidosis. This variant was not found in affected Domestic Longhair cats, evidencing genetic diversity in this disease among different cat lines, suggesting that other mutations may be responsible in other feline breeds.
Most affected breeds
Persian
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