Glycogen storage disease type I (GSDI), also called von Gierke disease, is a rare inherited disorder characterised by the accumulation of glycogen in cells, particularly in the liver, kidneys, and small intestines. This buildup interferes with normal organ function and causes various health complications.
There are two main types of GSDI, classified based on their genetic causes and symptoms: glycogen storage disease type Ia (GSDIa) and type Ib (GSDIb). Previously, two additional forms, called types Ic and Id, were described. However, these are now recognised as variations of GSDIb. GSDIa arises through mutations in the G6PC gene that cause a deficit of the catalytic subunit G6P-alpha expressed in the liver, kidney and intestine which results in a buildup of glycogen in the cells.
GSDI results from mutations in two genes: G6PC1 and SLC37A4. Mutations in G6PC1 cause GSDIa, while mutations in SLC37A4 lead to GSDIb.
Symptoms of GSDI typically manifest at around 3 to 4 months of age; these may include hypoglycemia (low blood sugar), lactic acidosis, hyperuricemia (high uric acid levels), and hyperlipidemia (elevated blood fats). Other features include an enlarged liver and kidneys, short stature, thin limbs, and a protruding abdomen. In GSDIb, additional issues such as neutropenia (low white blood cell count), frequent infections, oral problems, and inflammatory bowel disease are common. Adolescents and adults may develop osteoporosis, gout, kidney disease, and benign liver tumours which may progress to cancer.
