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Pompe Disease (GSDII; Glycogen Storage Disease II)
| Acronym: | GSDII, Pompe |
| Gene: | GAA |
| Mutation: | c.2237G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Canine Glycogen Storage Disease II (GSDII), also known as the Pompe disease, is an inherited disorder caused by a deficiency of a specific enzyme active in lysosomes. It is a part of a wider group of disorders known as glycogen storage diseases (GSDs) or glycogenosis, all characterized by defects in glycogen processing or breakdown within muscles, liver, or other cell types. GSDs can be divided into two types based on their cause, which can be genetic or acquired through intoxication. Acquired GSD has been identified only in cattle. Another classification of GSDs into different forms is based on the type of enzyme that is defective and in which body part the specific enzyme is usually active. Like this, there are about eleven GSD types, classified by a number, the name of the defective enzyme, or by the name of the doctor who first described the condition. Glycogen Storage Disease II (GSDII), or the Pompe disease, has been reported in humans and different animal species, such as Japanese quails, cats, sheep, and dogs. Canine glycogen storage disease is known to affect Lapponian dog breeds, such as the Finnish and Swedish Lapphunds and the Lapponian Herder. It was for the first time described in a Swedish Lapland dog in 1970, but the genetic cause of the Pompe disease in dogs was not known until 40 years later.
Acid alpha-glucosidase, also known as acid maltase, is an enzyme active in lysosomes, where it is usually involved in reactions of glycogen and maltose break down into glucose, a simpler sugar and a main source of energy in the body. When this enzyme becomes inactive or defective, the breakdown of glycogen does not occur, which causes its build-up in the cells. High concentrations of built-up glycogen are toxic, which causes organ and tissue damage in the whole body, especially in muscles, resulting in the development of symptoms of Pompe disease. First clinical signs in affected dogs are observable at around 6 months of age. The symptoms include poor growth, vomiting, progressive muscular weakness, condition loss, heart disease, and myocardial hypertrophy. Due to the severity of symptoms, death occurs before 2 years of age in affected dogs, or euthanasia is required. Pathological findings reveal glycogen accumulation in the cerebral cortex, liver, and myocardial plus esophageal smooth muscle. Severe acid alpha-glucosidase enzyme activity deficiency is registered in the heart, skeletal muscle, and liver.
Glycogen Storage Disease II (GSDII), or the Pompe disease, is caused by a mutation of the GAA gene (acid alpha-glucosidase), which causes the expression of the defected enzyme, resulting in the development of Pompe disease. Canine Pompe disease is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the GSDII symptoms. When mating two carriers (heterozygotes) at conception each cub 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:
Seppälä EH, Reuser AJJ, Lohi H. A Nonsense Mutation in the Acid α- Glucosidase Gene Causes Pompe Disease in Finnish and Swedish Lapphunds. PLoS ONE 8(2): e56825, 2013.
Walvoort HC, Dormans JA, van den Ingh TS. Comparative pathology of the canine model of glycogen storage disease type II (Pompe’s disease). J Inherit Metab Dis 8:38-46, 1985.
Walvoort HC, Slee RG, Sluis KJ, Koster JF, Reuser AJ. Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid alpha-glucosidase deficiency). Am J Med Genet 19:589-98, 1984.