GBE1-related disorders are a group of conditions caused by a deficiency in the glycogen branching enzyme (GBE), leading to abnormal glycogen accumulation in tissues.
The severity and onset of symptoms depend on the degree of GBE deficiency and can be categorized into two major forms: glycogen storage disease IV (GSD IV) and adult-onset polyglucosan body disease (APBD).
Glycogen Storage Disease IV (GSD IV):
Hepatic Subtype: Common in infants, symptoms include poor weight gain, muscle weakness, and enlarged liver. Cirrhosis often develops, leading to liver failure and death by age 5. In some cases, symptoms may appear during childhood without worsening liver disease.
Neuromuscular Subtype: Involves muscle weakness and heart disease, with varying severity. Severe cases present at birth with muscle weakness, enlarged heart, and breathing difficulties, leading to early death. Onset in late childhood can result in mild or severe, progressive disease, leading to death in the third decade.
Adult-Onset Polyglucosan Body Disease (APBD):
Symptoms typically emerge after age 40 and include difficulty walking, bladder control issues, and mild cognitive impairments related to memory, problem-solving, and planning. Often misdiagnosed due to symptom overlap with other conditions like multiple sclerosis.
There is no cure for these disorders, and treatment focuses on symptom management through physical therapy and proper nutrition. Liver transplantation may extend the lifespan in some cases of hepatic GSD IV, but outcomes are variable, with limited data available. Transplantation complications or progression of GSD symptoms, particularly heart failure, can affect outcomes in these cases.
This group of conditions is caused by pathogenic (disease-causing) variants in the GBE1 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 68 chance to be a carrier.