G6PC-related conditions are inherited in an autosomal recessive manner. A positive result means that a pathogenic (disease-causing) or likely pathogenic variant was found in both copies of the G6PC gene. A carrier result means that a pathogenic or likely pathogenic variant was found in one copy of the G6PC gene. Carriers for G6PC-related conditions usually have no symptoms of the condition. Variants in the G6PC gene are associated with Glycogen Storage Disease, Type 1a (GSD1a). Features of GSD1a may vary from person to person.
GSD1a is an inherited disorder caused by the buildup of a certain type of sugar, glycogen, and fat in the cells of the body, particularly in the liver, kidneys, and intestines. This glycogen and fat buildup impairs the ability of the organs to function normally. Signs and symptoms usually appear in infancy, around 3 or 4 months of age. Affected infants may have low blood sugar (hypoglycemia), which can lead to seizures, a buildup of lactic acid in the body (lactic acidosis), high blood levels of a waste product called uric acid (hyperuricemia), and excess amounts of fats in the blood (hyperlipidemia). They may also have diarrhea and deposits of cholesterol in the skin (xanthomas). As they get older, children with untreated GSD1a have short stature with thin arms and legs, enlarged liver, and in some cases, enlarged kidneys. Some patients have problems with blood clotting and have episodes of bleeding, including nosebleeds (epistaxis). A variety of long-term complications can occur with GSD1a including delayed puberty, thinning of the bones (osteoporosis), arthritis resulting from uric acid crystals in the joints (gout), pancreatitis, systemic high blood pressure (hypertension), and high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Females may also have abnormal ovaries (polycystic ovaries). Changes in neurologic function can also occur, particularly in patients with poor dietary compliance. In affected teens and adults, tumors called adenomas may form in the liver. Adenomas are usually noncancerous (benign), but can occasionally become cancerous (malignant).
Kidney disease is a common feature of GSD1a. Accumulation of glycogen and fat can lead to renal enlargement and affect kidney function, leading to symptoms such as protein in the urine (proteinuria), a buildup of calcium in the kidney tissue (nephrocalcinosis), and kidney stones. Some individuals with GSD1a progress to end-stage renal disease (ESRD) and may require a renal transplant.
Medical treatment is available for GSD1a, including dietary changes and nutrient supplementation. Early diagnosis and initiation of treatment can help prevent or lessen some of the symptoms of GSD1a, and greatly improves the life expectancy of individuals with GSDI. However, long-term complications, including progressive renal failure, can still occur.