Mutations in this gene are associated with glycogen storage disease type IV (also known as Andersen's disease) in newborns and with adult polyglucosan body disease.
Approximately 40 mutations in the GBE1 gene, most resulting in a point mutation in the glycogen branching enzyme, have led to the early childhood disorder, glycogen storage disease type IV (GSD IV).  This disease is characterized by a severe depletion or complete absence of GBE, resulting in the accumulation of abnormally structured glycogen, known as polyglucosan bodies.  Glycogen buildup leads to increased osmotic pressure resulting in cellular swelling and death.  The tissues most affected by this disease are the liver, heart, and neuromuscular system, areas with the greatest levels of glycogen accumulation.  Abnormal glycogen buildup in the liver interferes with liver functioning and can result in an enlarged liver and liver disease.  In muscles, the inability of cells to efficiently breakdown glycogen due to the severe reduction or absence of branching can lead to muscle weakness and atrophy.  
At least three mutations in the GBE1 gene have been found to cause another disease called adult polyglucosan body disease (APBD).  While in GSD IV GBE activity is undetectable or minimally detectable, APBD is characterized by reduced or even normal GBE activity. In this disease, abnormal glycogen can build up in neurons leading to a spectrum of problems. Specifically, some disease characteristics are gait difficulties from mixed upper and lower motor neuron involvement sensory loss in lower extremities, and neurogenic bladder, a problem in which a person lacks bladder control due to a brain, spinal cord, or nerve condition.