Glycogen Storage Disease: Type Ia

Glycogen storage disease type Ia (GSD Ia) is an inherited disorder caused by the deficiency of an enzyme called glucose-6-phosphastase that prevents the body from completely breaking down food into energy. With defective enzyme function, individuals with GSD type Ia cannot maintain blood glucose levels during fasting and will develop low blood sugar. Symptoms become obvious as early as three to four months after birth and affected infants commonly present with low blood sugar, seizures, high lactic acid level, high uric acid and lipid levels in blood and enlarged liver. As they grow older, poor height and weight growth is noted. Kidney disease, high blood pressure in the lungs and decreased bone density are complications that can also occur as individuals grow older. With proper dietary management and careful medical surveillance, GSD Ia patients can live a normal lifespan. GSD Ia is caused by pathogenic variants in the G6PC gene.

GSD Ia 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 no signs or symptoms associated with being a carrier for GSD Ia. However, the risk to have a child affected with the disease is increased. Testing of reproductive partners is recommended for carriers of GSD Ia.

GSD Ia is common in the Ashkenazi Jewish population with a frequency of 1 in 20,000 newborns. This disorder is relatively rare in the general population, occurring in 1 in 100,000 newborns.

Genetics Home Reference: Glycogen storage disease type Ia (http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i)
Association for Glycogen Storage Disease (http://www.agsdus.org/)

Gene Reviews: Glycogen Storage Disease Type I (http://www.ncbi.nlm.nih.gov/books/NBK1116/)
OMIM [Glycogen Storage Disease Type Ia: 232200] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing