What is the Classification/Types of Forbes Disease?
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.
What is the 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.
What is the Classification/Type of Forbes Disease?
Glycogen storage disease type III or Forbes disease is classified into four subtypes. These are as follows:
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.
GSD-IIIc is extremely rare and is believed to be caused by a loss of activity of glucosidase catalytic site of glycogen debranching enzyme. This affects both liver and muscles.
GSD-IIId is also considered extremely rare and is suspected to be caused by loss of activity of transferase catalytic site of the glycogen debranching enzyme. This disease affects only liver of individuals, not the muscles.
What are the 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 (enlarged liver in about 98% cases), hypoglycemia (low blood sugar in about 53% cases), failure to grow (in about 49% cases) and recurrent illness and/or infection (in about 17% of all cases). 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 slowed hypoglycemia, 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 Diagnosis and Treatment for Forbes Disease?
The diagnoses of Forbes disease include CBC, biopsy of muscle or liver and ultrasound. It can further be confirmed by genetic testing for mutation of AGL gene.
The basic treatment of Forbes disease is dietary modification, which 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 consume uncooked starch supplements such as cornstarch. The patient should also monitor his/her 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.