Alpha-Mannosidosis Persian Cat Type (AMD)

54.90 € inc. Vat

Acronyms: AMD
Gene: MAN2B1
Mutation Deletion
Mode of inheritance: Autosomal recessive
Breeds: Persian

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Product Description

Alpha-Mannosidosis Persian Cat Type (AMD)

Alpha-Mannosidosis Persian Cat Type (AMD) is a form of feline Alpha-mannosidosis specific for Persian cat breed. Alpha-mannosidosis except cats is known to affect humans and cattle. Among cats, the disorder has been identified in domestic short-haired and long-haired kittens in different countries in European and North American continent. The disorder has been observed and reported as more severe and more progressive in Persian cats than in domestic long haired cats. Alpha-Mannosidosis is characterized by deficiency of lysosomal alpha-mannosidase (LAMAN) enzyme.

Enzyme alpha-mannosidase is located in the lysosomes, where it participates in complex sugars derived from glycoproteins break down. In case alpha-mannosidase enzyme is defective, the large sugar molecules, oligosaccharides, build up inside the cell, causing its impairment. This has biggest impact on the central nervous system, resulting in its detoration.

Characteristics and Symptoms

Age of symptoms onset is variable among affected cats, depending on degree of enzyme’s deficiency, but is most commonly between 7 and 15 months of age. Reported clinical signs are ataxia (uncoordinated walking), intention tremors, skeletal abnormalities, retarted growth, ocular abnormalities such as corneal and lenticular opacities, and hepatomegaly. Behavioral abnormalities have been observed, such as running in circles, jumping without provocation, dementia, apathy and poor appetite. Other findings included radiographic abnormalities of the spine and long bones, cataracts and tapetal changes, hepatomegaly, lymphadenopathy, and thickened peripheral nerves. Measured activity of alpha-mannosidase in affected kittens is less than 2% of the normal activity, while in carriers (heterozygotes), the measured activity is less than 50% of the normal one. In affected kittens stillbirths and neonatal deaths are very common, and most do not survive more than 6 months.

Biopsies reveal severe vacuolization of neurons and glial cells of the nervous system, as well as in spinal and enteric ganglia. In peripheral nerves of the central nervous system, numerous vacuolated macrophages are present. Cerebral white matter appears as poorly myelinated. In larger neurons lipofuscin-like inclusions are observed.

Genetics

Alpha-Mannosidosis Persian Cat Type (AMD) is associated to mutation in lysosomal alpha-mannosidase gene (LAMAN), causing expression of deficient enzyme.

The disorder is inherited is an autosomal recessive pattern. Cat carrying one copy of the mutated gene is heterozygous and will not show the Alpha-Mannosidosis symptoms. When mating two carriers (heterozygotes) at conception each kitten has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

References:

Berg, T. et al. (1997.): Purification of feline lysosomal a-mannosidase, determination of its cDNA sequence and identification of a mutation causing a-mannosidosis in Persian cats. Biochem. J. 328, 863-870.

Alroy, J. et al. (1988.): Alpha-Mannosidase Deficiency in Persian Cats: A Model of Human Alpha-Mannosidosis. Volume 150 of the series NATO ASI Series pp 649-659.

Cummings, J. F., Lahunta, A., Boeuf, L. Le (1988): The clinical and pathologic heterogeneity of feline alpha-mannosidosis. J Vet Intern Med. 2(4): 163-70.