Glycogen storage disease type II (NORD)

Pompe disease, also called glycogen storage disease type II, is a genetically inherited condition caused by insufficient functioning of an enzyme called lysosomal acid alpha-1,4-glucosidase, or just acid alpha-glucosidase, and it’s caused by a mutation of the GAA gene. It’s named after the Dutch pathologist, Dr. J.C. Pompe, who first described it in 1932.

Glucose is used for energy by most cells of the body, and it’s stored inside the cells as a compact, branch-shaped molecule called glycogen. When a cell needs energy, it uses enzymes to remove glucose molecules from the branches. One of the organelles within the cell is the lysosome, which functions a bit like a tiny recycling plant. The lysosome contains enzymes that break down cellular substances so that they can be recycled. Now for some reason, and it’s not really understood why, but small amounts of glycogen end up in the lysosomes, where it’s broken down by an enzyme called acid alpha-glucosidase, to release glucose from the glycogen chain.

In Pompe disease, a mutation of the GAA gene prevents the production of enough functional acid alpha-glucosidase, and as a result, lysosomes can’t break down glycogen. This leads to a buildup of glycogen within the cytoplasm and lysosomes, and that leads to cellular damage and destruction.

Now, normally, glycogen is found in the largest amounts in the cytoplasm of liver cells and all three types of muscle cell. In individuals with Pompe, glycogen mostly accumulates in the lysosomes of those cells. Skeletal muscles include various muscles of the body as well as the diaphragm which is the primary breathing muscle. Cardiac muscle makes up the majority of the heart, and smooth muscle is found in the walls of blood vessels and many other organs.

Pompe disease is an autosomal recessive condition - so in other words, both parents must be carriers. The severity of the condition depends on how much functional acid alpha-glucosidase is produced. If little to no enzyme exists, the infantile-form of the condition typically occurs. Within the first few months of life, muscular damage to the heart develops, causing hypertrophic cardiomyopathy or an enlarged heart and eventual heart failure. Skeletal muscle weakness causes severely decreased muscle tone of the entire body. Weakness of the diaphragm and other breathing muscles lead to respiratory failure as well. Other findings include an enlarged liver which is thought to be largely due to heart failure, and a large tongue, which is primarily made of muscle.