GBR-13069

Glycogen Storage Disease Type I

Diagram illustrating the biochemical pathway affected in Glycogen Storage Disease Type I.

Glycogen Storage Disease Type I (GSD I), also known as von Gierke disease, is a metabolic disorder characterized by the accumulation of glycogen in the liver and kidneys due to a deficiency in the enzyme glucose-6-phosphatase. This enzyme is crucial for the final step of gluconeogenesis and glycogenolysis, which is the conversion of glucose-6-phosphate into free glucose.

Pathophysiology

GSD I is caused by mutations in the G6PC gene, which encodes the glucose-6-phosphatase enzyme. The deficiency of this enzyme leads to the inability to convert glucose-6-phosphate into glucose, resulting in the accumulation of glycogen and fat in the liver and kidneys. This accumulation causes hepatomegaly and nephromegaly, and the inability to maintain normal blood glucose levels leads to hypoglycemia.

Clinical Features

Patients with GSD I typically present in infancy with symptoms such as severe hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. The hypoglycemia can lead to seizures and developmental delay if not managed properly. Other features include a "doll-like" facial appearance, short stature, and delayed puberty.

Diagnosis

The diagnosis of GSD I is based on clinical presentation, biochemical tests, and genetic testing. Biochemical tests reveal hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. Genetic testing can confirm mutations in the G6PC gene.

Management

Management of GSD I focuses on maintaining normal blood glucose levels to prevent hypoglycemia. This is achieved through frequent feedings of cornstarch and a high-carbohydrate diet. In some cases, allopurinol is used to manage hyperuricemia, and lipid-lowering agents may be used to control hyperlipidemia.

Prognosis

With proper management, individuals with GSD I can lead relatively normal lives, although they may have an increased risk of developing hepatic adenomas and renal disease later in life.

Related Pages

• Glycogen Storage Disease
• Metabolic Disorder
• Gluconeogenesis
• Glycogenolysis