Reviewed By: Pramod Kerkar, MD, FFARCSI

Forbes disease is an inherited disorder due to the deficiency of amylo-1,6-glucosidase that results in the accumulation of abnormal glycogen (limit dextrin) in liver and muscles. Forbes disease is a type of glycogen storage disease that has various names such as glycogen storage disease type III, Cori’s disease, amylo-1,6-glucosidase deficiency, AGL deficiency, glycogenosis type III, limited dextrinosis, glycogen debrancher deficiency and GSD-III. Forbes disease is a rare hereditary disease, which affects one in 100,000 people all around the world, 1 in 40,000 in the United States, but is common in the Inuit population of Canada, Faroese and North African Jews.

Cause of Forbes Disease

The main cause of glycogen storage disease type III or Forbes disease is the mutation of AGL gene located on chromosome 1p21. It is a genetic disorder that is inherited as an autosomal recessive trait. AGL gene is responsible for the production of amylo-1,6-glucosidase debranching enzyme, and the lack of this enzyme leads to incomplete break down of glycogen. This causes insufficient production of glucose in the body, thus insufficient energy is produced. The incompletely broken down glycogen structure is known as limit dextrin and is stored in liver and muscle (skeletal and cardiac) tissues. The risk is the same for males and females. The risk also increases when both the parents are closely related than in unrelated parents.

Symptoms of Forbes Disease

Generally, the symptoms of Forbes disease start at very early age (as early as one year of age) as it is a genetic disorder. The most common symptoms of the disease are hepatomegaly, hypoglycemia, enlarged abdomen, weak/flaccid muscles, failure to grow and recurrent illness and/or infection. Other symptoms of Forbes disease include hyperlipidemia, fasting intolerance, frequent nosebleeds, difficulty fighting infections, cardiac hypertrophy. They also include short stature, delayed puberty, retarded growth, failure to thrive, underdeveloped midface, deep set eyes, depressed nose bridge, broad nose tip, upturned nose tip, bow shaped lips, muscle weakness that progressively worsens with age, wasting of muscles of hands and feet along with myopathy (both of which are seen late in life).

Can you Prevent Forbes Disease?

Forbes disease, as we know by now is an inherited disease due to an autosomal recessive trait, which causes mutation in the AGL gene. This means that once an individual inherits both the copies of the gene from each parent (both the parents are carriers of the disease) then one is definitively going to inherit the disease and in such a case, it cannot be prevented once the disease is inherited. It can; however, be prevented when both the parents get gene mapping done before the birth of their offspring to check whether they are carriers of the defective gene or not and can take gene counseling and consultation as to the possible scenarios of the situation. It can also be avoided by not marrying in close relations. When someone in family has Forbes disease or if an individual has it, then one can consult a geneticist to discuss the likelihood of their children having the disease.

In pregnant women, early testing can be carried out by taking a sample of amniotic fluid to study the enzymes or proteins in the amniotic fluid to determine whether the unborn baby will have Forbes disease in future. However, once Forbes disease is inherited the only way is to limit the progression of the disease through dietary modification. Dietary management includes high protein diet and avoiding fasting to keep hypoglycemia at bay. Nocturnal nasogastric feeding tube may be required for the prevention of hypoglycemia (low blood sugar level) during sleep. Patients should take frequent meals and include starch supplement such as cornstarch in their diet to keep blood glucose level normal. The patient should also monitor one's blood glucose level and ketone level. The dietary modification is known to limit and prevent heart and/or muscular disease. In patients with severe hepatic cirrhosis, liver failure and hepatocellular carcinoma, liver transplantation is the only option.

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Pramod Kerkar

Written, Edited or Reviewed By:

, MD,FFARCSI

Pain Assist Inc.

Last Modified On: July 23, 2018

This article does not provide medical advice. See disclaimer

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