Glycogen Storage Disease Type II, Pompe disease (Glycogen storage disease type II, Pompe disease) - Gen GAA

Pompe disease, also known as glycogenosis type II, is an inherited disorder due to accumulation of glycogen in the body cells. Glycogen accumulation in certain organs and tissues, especially in muscles, alters its ability to function normally. They described three types of Pompe disease, which differ in severity and the age at which they occur. These types are known as classic or childhood - onset, non - classical form of childhood - onset and late - onset form.

The classic form of childhood - onset begins a few months after birth. Children with this disorder tend to have myopathy, hypotonia, hepatomegaly, and heart defects. In addition, they may fail to gain weight, have stunted growth and respiratory problems. If left untreated, it leads to death from heart failure in the first year of life.

Nonclassical form of childhood onset, usually manifests from the first year of age, and is characterized by delayed motor skills and progressive muscle weakness. In addition, affected individuals may have cardiomegaly, but not usually have heart failure. Muscle weakness in this disorder causes severe respiratory problems and, most children with no classic infantile onset disease live only during early childhood.

The late - onset form may not become evident until after childhood, adolescence or adulthood. This form is usually milder than childhood - onset forms and is less likely to affect the heart. Most individuals with late - onset form manifest progressive muscle weakness, especially in the legs and trunk, including the respiratory muscles. As the disease progresses, respiratory problems may lead to respiratory failure.

This process is due to mutations in the GAA gene (alpha glucosidase, acid), located on the long arm of chromosome 17 (17q25.2-q25.3). This gene encodes an enzyme called alpha-glucosidase, also known as acid maltase. This enzyme is active in lysosomes, and decomposes glycogen into glucose, which is the main source of energy for most cells.

There are more than 200 mutations in the GAA gene responsible for Pompe disease. Many of these mutations change an amino acid alpha-glucosidase. Other mutations inserted or deleted nucleotides in the gene. Mutations in this gene significantly reduce the activity of acid alpha-glucosidase. Consequently, glycogen accumulates to toxic levels in the lysosomes. This buildup damages the organs and tissues throughout the body, including the muscles, leading to progressive signs and symptoms of Pompe disease.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Type II (Pompe disease) glycogenosis, by complete PCR amplification of the exons of the GAA gene and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).