GSD1d

Glycogen storage disease type Ib, also known as GSD1b or GSD Ib, is a rare inherited metabolic disorder. It is a form of von Gierke disease, specifically GSD type I, and is characterized by a deficiency in the enzyme glucose-6-phosphatase translocase (G6PT). This enzyme is located in the membrane of the endoplasmic reticulum and is responsible for transporting glucose-6-phosphate into the endoplasmic reticulum. Once inside, glucose-6-phosphate can be converted to free glucose by glucose-6-phosphatase, which is then released into the bloodstream to maintain blood glucose levels.

The deficiency in G6PT activity leads to a buildup of glucose-6-phosphate in liver and kidney cells. This impairs the liver's ability to release glucose into the blood, resulting in hypoglycemia, particularly during fasting. Affected individuals often present in infancy or early childhood with symptoms such as severe hypoglycemia, seizures, enlarged liver (hepatomegaly), and failure to thrive. They may also experience lactic acidosis and hyperuricemia.

In addition to the metabolic derangements seen in GSD1a, individuals with GSD1b also have neutropenia, which is a low count of neutrophils, a type of white blood cell. This neutropenia predisposes them to recurrent bacterial infections, which can be severe and life-threatening. Other complications can include platelet dysfunction leading to bleeding tendencies, kidney disease, and growth retardation.

The diagnosis of GSD1b is typically made based on clinical presentation, biochemical tests showing hypoglycemia and elevated lactate and uric acid, and genetic testing to confirm mutations in the SLC37A4 gene, which encodes the G6PT enzyme. Management focuses on preventing hypoglycemia through frequent feeding and uncooked cornstarch administration. Treatment of neutropenia and infection is also crucial and may involve granulocyte colony-stimulating factor (G-CSF). Liver transplantation is a potential treatment option for severe cases unresponsive to medical management.