Reviewed By: Pramod Kerkar, MD, FFARCSI

Forbes disease is a rare 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.

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 leads to 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, failure to grow and recurrent illness and/or infection. There is also protrusion of abdomen due to hepatomegaly along with weak/flaccid muscles during childhood. Hepatomegaly, starts subsiding with age as the child becomes adult; however, it may progress to liver cirrhosis, liver failure and hepatic carcinoma. 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).

What Is The Outlook For Forbes Disease?

Forbes disease is a multisystem genetic disorder affecting liver, skeletal muscles and heart and should be managed with multidisciplinary approach including primary care provider, biochemical geneticist, metabolic specialist, cardiologist, hepatologist, neuromuscular specialist, gastroenterologist, physical therapist, occupational therapist, genetic counselor and metabolic dietitian depending on the disease manifestation for best therapy and outcome for patients. The outlook or prognosis of Forbes disease is variable according to different patients and depends on the organs involved and the severity of the disease. GSD-IIIa subtype is the most common affecting nearly 85% of individuals and affects both the liver and muscles (cardiac and/or skeletal). GSD-IIIb affects about 15% of all individuals and affects only the liver.

With the advancement in therapy, the outlook on Forbes disease has drastically improved. Dietary modification is very effective in the management of the disease. This includes high protein diet, avoiding fasting and frequent meals to keep hypoglycemia at bay. Nocturnal nasogastric feeding tube may be required for the prevention of hypoglycemia (low blood sugar level) during sleep. The use of uncooked starch supplements such as cornstarch as a source of continuous glucose source has drastically improved the prognosis of patient with the disease as they can live longer now. The patients should monitor their blood glucose levels and ketone levels. 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.

The newer possibilities of therapies and treatments are constantly emerging. Gene therapy, a small molecule therapy and enzyme replacement therapy are still debatable and need more studies and research, but with the advent of new treatments, the outlook of Forbes disease will be greatly improved.

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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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