Von Gierke Disease

Glycogen storage diseases (GSDs) are autosomal recessive metabolic disorders resulting in storage of abnormal amounts and/or forms of glycogen. Von Gierke disease is a GSD caused by defective liver and kidney glucose-6-phosphatase activity and is named after the pathologist who first described excess glycogen storage in the liver. The disease-causing mutation(s) can be either in the gene coding for the liver glucose-6-phosphatase enzyme (G6PC) or in the gene coding for the endoplasmic reticulum substrate and/or product transport proteins of the glucose-6-phosphatase system. The two common forms of GSD1 are termed GSD1a and GSD1b, and are caused by deficiency in G6PC and the glucose-6-phosphate transporter (G6PT1), respectively. The disease is currently managed by nocturnal nasogastric infusion of glucose and/or cornstarch mixed into drinks during the day, but compliance is often low. Recent advances in the use of gene therapy in animal models of the disease provide hope for this approach in the treatment of human patients in the future.