To begin exploring how one's DNA can ultimately result in a genetic disease (phenotype) such as Pompe disease, what cellular processes are involved?
Pompe disease which occurs in 1 in 40,000 births is due to a mutation of a gene on chromosome 17 that makes an enzyme called acid alpha-glucosidase or GAA. This enzyme is used to break down glycogen, a storage product of glucose, found in muscles and the liver. This enzyme functions inside the cell's lysosomes. When glycogen enters the lysosome along with GAA, it is converted to glucose and this can be used for cellular energy in respiration. In Pompe disease, a mutation in this gene can reduce or eliminate the function of GAA. Glycogen accumulates in the body and it particularly affects the heart and skeletal muscle cells. Over 300 different mutations have been identified in this gene that can cause a disease phenotype. Early onset occurs at the beginning of life where the individual has almost no GAA. Most babies die of cardiac arrest or breathing problems. Late onset is a partial defiiciency of GAA. Muscle weakness and respiratory problems can lead to death. Besides getting helps from cardiologists, respiratory doctors and others specialists, new drugs have been developed. Enzyme replacement therapy has been able to decrease heart size, help muscles work, and restore heart function.