Canine Glycogen Storage Disease II (GSDII) – Pompe Disease
Canine Glycogen Storage Disease II (GSDII), also known as the Pompe disease, is an inherited disorder caused by 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 cells types. GSDs can be divided in 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 type of enzyme that is defected 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 first tie 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.
Characteristics and Symptoms
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 defected, break down of glycogen does not occur, which causes its build up in the cells. High concentrations of built up glycogen are toxic, which causes organs and tissue damages in whole body, especially in muscles, resulting in 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 severity of symptoms, death occurs before 2 years of age in affected dogs, or euthanasia is required. Pathological findings reveal glycogen accumulation in cerebral cortex, liver, and lyocardial plus esophageal smooth muscle. Severe acid alpha-glucosidase enzyme activity deficiency is registered in heart, skeletal muscle and liver.
Glycogen Storage Disease II (GSDII), or the Pompe disease, is caused by a mutation of GAA gene (acid alpha-glucosidase), which causes expression of defected enzyme, resulting in development of Pompe disease.
Canine Pompe disease is inherited as an autosomal recessive disorder. 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.
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.