Glycogen Storage Disease Type III

Glycogen storage disease type III (GSD3) is an inherited disorder that results from an accumulation of a complex sugar (glycogen) in many organs of the body, most particularly the liver and muscles. This is due to a defective enzyme called the glycogen debranching enzyme. There are four subtypes of GSD III; GSD IIIa, GSD IIIb, GSD IIIc, and GSD IIId. GSD IIIa and IIb are the most common. Beginning in infancy, individuals with GSD III can have low blood sugar, elevated blood levels of liver enzymes, and excess amounts of fats in the blood. Typically individuals develop an enlarged liver as they get older, which may develop into chronic liver disease and ultimately liver failure. Growth is often affected because of the liver problems. The majority of individuals affected with GSD IIIa have weakened muscles, affecting both the heart and skeletal muscles, usually appearing in early childhood and is slowly progressive. GSD IIIc and GSD IIId are extremely rare. Good dietary control can prevent most of the symptoms associated with GSD3. GSD3 is caused by pathogenic variants in the AGL gene.

GSD3 is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for GSD3. However, the risk to have a child affected with GSD3 is increased. Testing of reproductive partners is recommended for carriers of GSD3.

GSD3 disease affects all ethnicities but it is more common in individuals from the Faroe Islands, occurring in 1 in 3600 newborns and the North African Jewish population, occurring in 1 in 5400 newborns. In the United States, it is estimated to affect 1 in 100 000 newborns.

Genetics Home Reference: Glycogen storage disease type III (GSD III) (http://ghr.nlm.nih.gov/)
Association for Glycogen Storage Disease: Glycogen storage disease type III (GSD III) (http://www.agsdus.org/index.html)

OMIM [Glycogen storage disease type III (GSD III): 232400] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Glycogen storage disease type III (GSD III) (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing