Alpha-mannosidosis is a hereditary lysosomal storage disease of the Persian cat, caused by a deficiency of the enzyme acid alpha-mannosidase (MAN2B1 gene). The defect prevents the breakdown of oligosaccharides, which accumulate in neurons and other cells, producing progressive neurodegeneration. Affected kittens develop ataxia, tremors and general deterioration in the first months of life, progressing to death or euthanasia. There is no treatment and control is based on avoiding matings between carriers.

Very rare disease. Classically described in the Persian cat and in short-haired domestics of certain populations. There are no current carrier frequency figures (limited data); current cases are sporadic.

- Signs from the first weeks or months of life\n- Progressive ataxia with hypermetria and a wide stance\n- Intention tremors, especially of the head and neck\n- Corneal opacity in some cases\n- Stunted growth and general deterioration\n- Behavioural changes and apathy\n- Opisthotonus and seizures in advanced stages\n- Death or euthanasia usually in the first or second year of life

Feline alpha-mannosidosis was described in the late 1970s and early 1980s in cats from New Zealand and in other series (Burditt et al., 1980; Abraham et al., 1983), both in Persians and domestics, and became a classic natural animal model of human alpha-mannosidosis. Biochemical studies demonstrated the acid alpha-mannosidase deficiency with urinary excretion of oligosaccharides and storage vacuoles in multiple tissues. Berg et al. (1997) purified the feline enzyme, determined its cDNA and identified a 4-bp deletion in MAN2B1 as the cause of the Persian cat form.

- Test Persian breeding animals from lines with a history of early ataxic kittens\n- Never mate carrier with carrier: 25% risk of affected kittens\n- A carrier can be mated to a clear animal, keeping only clear offspring for breeding if you aim to eliminate the allele\n- With kittens showing progressive ataxia and tremors, first rule out infectious and metabolic causes and request a workup for storage diseases\n- Record the results together with the pedigree at the breed club

The differential diagnosis includes other feline storage diseases (type IV glycogenosis, mucopolysaccharidosis, lipofuscinosis), cerebellar abiotrophies and infectious or toxic encephalopathies. Laboratory workup relies on urinary excretion of oligosaccharides, vacuoles in lymphocytes on the blood smear and deficient alpha-mannosidase activity in leukocytes; DNA testing confirms the status. There is no effective treatment (bone marrow transplantation has been experimental); management is palliative and genetic counselling is mandatory after a case.

1. Burditt LJ et al. 1980. Biochemical studies on a case of feline mannosidosis. Biochem J. PMID: 7213340
2. Abraham D et al. 1983. The catabolism of mammalian glycoproteins. Comparison of the storage products in bovine, feline and human mannosidosis. Biochem J. PMID: 6661184
3. Raghavan S et al. 1988. Characterization of alpha-mannosidase in feline mannosidosis. J Inherit Metab Dis. PMID: 3128686
4. Berg T et al. 1997. Purification of feline lysosomal alpha-mannosidase, determination of its cDNA sequence and identification of a mutation causing alpha-mannosidosis in Persian cats. Biochem J. PMID: 9396732
5. Vite CH et al. 2001. Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis. J Neuropathol Exp Neurol. PMID: 11487056
6. Sun H et al. 1999. Retrovirus vector-mediated correction and cross-correction of lysosomal alpha-mannosidase deficiency in human and feline fibroblasts. Hum Gene Ther. PMID: 10365662
OMIA000625-9685.