Glycogen Storage Disease, Type IV / Adult Polyglucosan Body Disease (GBE1)
Glycogen storage disease, type IV is an autosomal recessive disorder that is caused by pathogenic variants in the gene GBE1. It is found in individuals of many different ethnicities, but is more prevalent in individuals of Ashkenazi Jewish descent. The disease presentation can be quite variable. In the classic form, individuals appear well at birth but rapidly deteriorate due to progressive liver disease. Patients may also have cardiomyopathy and hypotonia. Development of liver cirrhosis necessitates a liver transplant by age of five years. The other subtypes vary in their age of onset and severity; several result in a more severe phenotype with death in early infancy, and others develop later in childhood and generally have a better prognosis. Pathogenic GBE1 variants can also cause a disease known as adult polyglucosan body disease, in which slowly progressive neurologic symptoms begin in middle age, including cognitive impairment, difficult walking, sensory loss, and difficulty controlling the bladder. While loose genotype-phenotype correlations have been reported, it may not be possible to determine the severity of the disease based on the patients genotype.
For information about carrier frequency and residual risk, please see the residual risk table.