DISEASE CHARACTERISTICS:
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. Some untreated neonates present with severe hypoglycemia; more commonly, untreated infants present at age three to four months with hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, and/or hypoglycemic seizures. Affected children typically have doll-like faces with fat cheeks, relatively thin extremities, short stature, and protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function can lead to a bleeding tendency with frequent epistaxis. Untreated GSDIb is associated with impaired neutrophil and monocyte function as well as chronic neutropenia after the first few years of life, all of which result in recurrent bacterial infections and oral and intestinal mucosal ulcers. Long-term complications of untreated GSDI include growth retardation and resulting short stature, osteoporosis, delayed puberty, gout, renal disease, pulmonary hypertension, hepatic adenomas with potential for malignant transformation, polycystic ovaries, pancreatitis, and changes in brain function. Normal growth and puberty may be expected in treated children. Many affected individuals live into adulthood.
DIAGNOSIS/TESTING:
The diagnosis of GSDI is based on clinical presentation, abnormal blood/plasma concentrations of glucose, lactate, uric acid, triglycerides, and lipids, and molecular genetic testing. Mutations in G6PC (GSDIa) are responsible for 80% of GSD1 and mutations in SLC37A4 (GSDIb) are responsible for 20% of GSD1. Molecular testing is clinically available for both genes.
MANAGEMENT:
Treatment of manifestations: Medical nutrition therapy to maintain normal glucose concentrations, prevent hypoglycemia, and provide optimal nutrition for growth and development. Allopurinol to prevent gout when dietary therapy fails to completely normalize blood uric acid concentration; lipid-lowering medications when lipid levels are elevated despite good metabolic control; citrate supplementation to help prevent development of urinary calculi or ameliorate nephrocalcinosis; angiotensin-converting enzyme (ACE) inhibitors to treat microalbuminuria; kidney transplantation for end-stage renal disease; surgery or other interventions such as percutaneous ethanol injections and radiofrequency ablation for hepatic adenomas; liver transplantation for patients refractory to medical treatment or with hepatocellular carcinoma; and treatment with human granulocyte colony-stimulating factor (G-CSF) for recurrent infections in GSDIb. Prevention of secondary complications: Improve hyperuricemia and hyperlipidemia and maintain normal renal function to prevent development of renal disease. Surveillance: Annual ultrasound examination of the kidneys and liver after the first decade of life; liver ultrasound examinations every three to six months if hepatic adenoma is detected. Agents/circumstances to avoid: Diet should be low in fructose and sucrose; galactose and lactose intake should be limited to one serving per day. Testing of relatives at risk: Molecular genetic testing (if the family-specific mutations are known) and/or evaluation by a metabolic physician soon after birth (if the family-specific mutations are not known) allows for early diagnosis and treatment of sibs at risk for GSDI.
GENETIC COUNSELING:
GSD1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Heterozygotes (carriers) are asymptomatic. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible by molecular genetic testing if both disease-causing alleles of an affected family member have been identified.
Copyright © 1993-2013, University of Washington, Seattle. All rights reserved.