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Alpha-Mannosidosis Persian Cat Type (AMD)
| Acronym: | AMD |
| Gene: | MAN2B1 |
| Mutation: | c.1749_1752del |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Alpha-Mannosidosis Persian Cat Type (AMD) is a form of feline Alpha-mannosidosis specific to the Persian cat breed. Alpha-mannosidosis except for 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 on the European and North American continents. 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 a deficiency of the lysosomal alpha-mannosidase (LAMAN) enzyme. Enzyme alpha-mannosidase is located in the lysosomes, where it participates in complex sugars derived from glycoproteins breakdown. In case the alpha-mannosidase enzyme is defective, the large sugar molecules, oligosaccharides, build up inside the cell, causing its impairment. This has the biggest impact on the central nervous system, resulting in its deterioration.
Age of symptoms onset is variable among affected cats, depending on the degree of enzyme deficiency, but is most commonly between 7 and 15 months of age. Reported clinical signs are ataxia (uncoordinated walking), intentional 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. The 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. Alpha-Mannosidosis Persian Cat Type (AMD) is associated with a mutation in the lysosomal alpha-mannosidase gene (LAMAN), causing the expression of deficient enzymes. The disorder is inherited in 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.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
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.