Andersen’s disease belongs to a group of rare genetic disorders of glycogen metabolism known as glycogen storage diseases. The lack of certain enzymes involved in the metabolism of glycogen leads to an abnormal accumulation of glycogen in various parts of the body, especially the liver and the muscles, which is known as glycogen storage disease. Glycogen is a complex carbohydrate that is converted into glucose for energy and hence is extremely important.
Andersen disease, also known as glycogen storage disease (GSD) type IV, is caused by the deficient activity of the glycogen-branching enzyme (GBE). This enzyme normally serves to increase the number of branch points during the formation of glycogen. However, in people with this disease, various specific mutations of the GBE gene have been identified. There is research ongoing to determine whether certain mutations may be associated with particular variants of the disease.
The genetics behind this disease
Andersen disease is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one 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 for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Signs & Symptoms
This disease is typically characterised by progressive internal scarring (fibrosis) and destruction of liver tissue (cirrhosis) leaving areas of nonfunctioning scar tissue and gradually impaired liver function. Initial signs and symptoms commonly include ‘failure to thrive (failure to grow and gain weight at the expected rate)’ and hepatosplenomegaly (abnormal enlargement of the liver and spleen).
The cirrhosis then leads to a chain reaction including:
High blood pressure in veins from the spleen and intestines to the liver (portal hypertension)
Abnormal fluid accumulation in the abdomen (ascites)
Enlargement of veins in the wall of the oesophagus (esophageal varices) which can also rupture causing vomiting of blood.
Liver failure
Abnormally reduced glucose levels (hypoglycemia)
Mental confusion and/or abnormalities
Jaundice
Diagnosis
Andersen disease is usually diagnosed or confirmed after birth (postnatally) during infancy or childhood (or, in some cases, adulthood), based upon:
Thorough clinical evaluation
Identification of characteristic physical findings
A complete patient and family history
Results of specialised tests (to check GBE activity and abnormalities)
Treatment
The treatment of Andersen’s disease is directed and aimed at specific symptoms. This includes therapies and medication for the associated cirrhosis, impaired liver function, neuromuscular disease and/or heart dysfunction. Treatment may commonly require dietary measures to maintain normal levels of glucose in the blood (normoglycemia) and provide sufficient nutritional intake in order to improve liver function and muscular strength. Another treatment option is a complete liver transplant. This however does not prevent abnormal buildup in the heart and muscles which leads to more complications. Some reports say that patients have not had any neuromuscular or heart complications but some reports suggest the buildup. Thus, further investigation is needed to determine the long-term safety and efficacy of liver transplantation and its effect on disease progression in classic Andersen disease.
More research and investigations are required to find a cure for the disease and not just treatments or therapies. However rare this disease is, it still affects 1 in 10000 people in the United States of America.
Written by: Svasti Tewari
Edited by: Sakshi Deshpande
Citations:
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