Forbes disease (GSD-III) is one of several glycogen storage disorders (GSD) that are inherited as autosomal recessive traits. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase (debrancher enzyme). This enzyme deficiency causes excess amounts of an abnormal glycogen (the stored form of energy that comes from carbohydrates) to be deposited in the liver, muscles and, in some cases, the heart.
There are two forms of this disorder. GSD-IIIA affects about 85% of patients with Forbes disease and involves both the liver and the muscles. GSD-IIIB affects only the liver.
Symptoms of Forbes disease, at least during the first 4 to 6 years of life, may be indistinguishable from another of the glycogen storage diseases, Von Gierke disease. The amount of glycogen in the liver and muscles is abnormally high and, because the liver is enlarged (hepatomegaly), the abdomen protrudes. The muscles tend to be flaccid.
A child with Forbes disease has a short stature, low blood sugar (hypoglycemia) that does not respond to the hormone glucagon, and an elevated level of fatty substances in the blood, known as hyperlipemia. Patients with Forbes disease may also have difficulty fighting infections, and may experience unusually frequent nosebleeds.
Some other individuals may have virtually no symptoms (asymptomatic) other than a protruding abdomen and an enlarged liver. These patients tend to lose these few symptoms during adolescence when their liver decreases progressively in size. Children with Forbes disease often grow slowly during childhood and puberty may be delayed, but their adult height is usually normal.
The defective gene responsible for GSD-III has been traced to Gene Map Locus 1p21, and the disorder is transmitted as an autosomal recessive trait. It is caused by lack of a debrancher enzyme (amylo-1,6-glucosidase) which is involved in the formation of the stored form of carbohydrates (glycogen). Glycogen is stored in the liver and muscles for future energy needs when it is converted into sugar (glucose). Glucose is used as a readily available source of energy. Without the debrancher enzyme, glycogen can only be broken down partially and the structure that is left, resembling a molecule called a “limit dextrin”, accumulates in liver and muscle tissues.
Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
All glycogen storage diseases together affect less than 1 in 40,000 persons in the United States. Forbes disease usually begins during childhood. It affects males as often as females. Patients with this disorder reported in Israel were generally of North African heritage.
The presence of Forbes disease is definitive if testing liver and muscle tissues (biopsies) for abnormal glycogen and debrancher enzyme is positive. White blood cells and connective tissue cells called fibroblasts can also be useful as a screen, but may not provide a definitive diagnosis.
Forbes disease is treated by continuous glucose delivery (intravenous drip) in order to avoid low blood sugar (hypoglycemia). Frequent small servings of carbohydrates and a high protein diet are advised during the day. At night, continuous tube feeding of food solutions such as Vivonex or polyglucose (glucose) may be administered to promote normal childhood growth.
Genetic counseling is helpful for families of children with Forbes disease and other glycogen storage diseases. People with this disorder can expect to live a normal life span. However, muscle disorders may develop with age.
Dr. Y.T. Chen at Duke University Medical Center, at the request of the Glycogen Storage Disease Association, is collecting DNA from patients with Glycogen Storage Disease Type I to form a DNA bank for GSDI. Interested patients may contact the Glycogen Storage Diseases Association for further information. The address and phone number of the organization are listed in the Resources section of this report.
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FROM THE INTERNET
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