Forbes Disease

Forbes disease, glycogen storage disease III, is one of numerous glycogen storage disorders (GSD). It effects about 1 in 100,000 individuals. It most frequently affects people of North African Jewish descent (1 in 5, 4000 individuals). The main cause of Forbes disease is the deficiency of the debrancher enzyme. Due to the deficiency, there is an excessive buildup of glycogen in the liver, heart and other muscles in the body. Glycogen is used in the body as energy however, due to the deficiency of the debrancher enzyme, in those with Forbes disease, glycogen is not able to break down completely and it begins accumulating in the liver and other muscles of the body. There are two types of Forbes disease: the first type is GSD IIIA which is about 90% of all cases of Forbes disease which affects the liver and the muscles. The other 10% have GSD IIIB which only the liver is affected.  In those with Forbes disease, there is a fault in chromosome 1p21. Forbes disease is an autosomal recessive trait meaning that two copies of the faulty gene (one from the moth and one from the father) are required in order to inherit this condition.
Classic symptoms may not be identifiable until the child is around 6 years old. Common symptoms include the enlargement of the liver (hepatomegaly), abnormal protrusion of the abdomen, flaccidity of the muscles, short stature, hypoglycemia (low blood sugar), accumulation of fatty substances which may lead to hyperlipidemia (a buildup of lipids in the blood), cirrhosis of the liver as well as others. Individuals with Forbes may develop myopathy (muscle weakness) which may affect the heart muscle. Some people with this disease may have a weakened heart muscle cardiomyopathy, and rarely hypertrophic cardiomyopathy but usually do not experience heart failure. Children with Forbes disease may have a compromised immune system and therefore have a tougher time fighting off infections.
In order to diagnose Forbes disease, liver function tests and muscle biopsies may be required to identify abnormal levels of glycogen in the body. Genetic testing may show the deficiency of the debrancher enzyme.
Treatment for Forbes disease may include IV (intravenous) glucose to prevent hypoglycemia. Infants and children are treated with a high protein diet every 3-4 hours. Good dietary control is also required. Home monitoring of glucose and ketone levels are required. Liver transplantation may be required and recommended for patients with severe liver cirrhosis, liver dysfunction, or liver cancer. Genetic counseling is recommended for families of children with GSDs.
Figure 1: Microscopic stained image of cells with Glycogen storage disease type III (Forbes Disease)