Glycogen storage diseases

Encyclopedia of Medicine, Apr 06, 2001 by Julia Barrett

Diagnosis usually occurs in infancy or childhood, although some milder types of GSD go unnoticed well into adulthood and old age. It is even conceivable that some of the milder GSDs are never diagnosed.

The four major symptoms that typically lead a doctor to suspect GSDs are low blood sugar, enlarged liver, retarded growth, and an abnormal blood biochemistry profile. A definitive diagnosis is obtained by biopsy of the affected organ or organs. The biopsy sample is tested for its glycogen content and assayed for enzyme activity. There are DNA-based techniques for diagnosing some GSDs from more easily available samples, such as blood or skin. These DNA techniques can also be used for prenatal testing.

Some GSD types cannot be treated, while others are relatively easy to control through symptom management. In more severe cases, receiving an organ transplant is the only option. In the most severe cases, there are no available treatments and the victim dies within the first few years of life.

Of the treatable types of GSD, many are treated by manipulating the diet. The key to managing GSD I is to maintain consistent levels of blood glucose through a combination of nocturnal intragastric feeding (usually for infants and children), frequent high-carbohydrate meals during the day, and regular oral doses of cornstarch (people over age 2). Juvenile and adult forms of GSD II can be managed somewhat by a high protein diet, which also helps in cases of GSD III, GSD VI, and GSD IX. GSD V and GSD VII can also be managed with a high protein diet and by avoiding strenuous exercise.

For GSD cases in which dietary therapy is ineffective, organ transplantation may be the only viable alternative. Liver transplants have been effective in reversing the symptoms of GSD IV.

Advances in genetic therapy offer hope for effective treatment in the future. This therapy involves using viruses to deliver a correct form of the gene to affected cells. Another potential therapy utilizes transgenic animals to produce correct copies of the defective enzyme in their milk. In late 1997, a Dutch pharmaceutical company, Pharming Health Care Products, began clinical trials to treat GSD II with human alpha-glucosidase derived from the milk of transgenic rabbits. Researchers at Duke University in North Carolina are also focusing on a treatment for Pompe's disease and, aided by Synpac Pharmaceuticals Limited of the United Kingdom, plan to begin clinical trials of a recombinant form of the enzyme in 1998.

People with well-managed, treatable types of GSD can lead long, relatively normal lives. This goal is accomplished with the milder types of GSD, such as Types VI, IX, and X. As the GSD type becomes more severe, a greater level of vigilance against infections and other complications is required. Given current treatment options, complications such as liver disease, heart failure, and respiratory failure may not be warded-off indefinitely. Quality of life and life expectancy are substantially decreased.