Key Points

• Glycogen storage diseases (GSDs) are inherited enzyme defects in glycogen synthesis or breakdown (Types I–XI).
• Type I (Von Gierke disease) results from glucose-6-phosphatase deficiency, causing severe fasting hypoglycemia and lactic acidosis.
• Management centers on maintaining normoglycemia through dietary therapy (frequent feeds, uncooked cornstarch) and treating metabolic complications.
• Long-term risks include hepatic adenomas, gouty arthritis, renal dysfunction, and growth delay.
• Early diagnosis and lifelong adherence to therapy markedly improve outcomes.

Introduction

Glycogen storage diseases are a heterogeneous group of autosomal recessive disorders caused by defects in enzymes involved in glycogen metabolism. Eleven types have been identified (GSD I–XI), each defined by the specific enzyme deficiency, clinical presentation, and tissue distribution of glycogen accumulation.

Classification of GSDs (Types I–XI)

• Type I: Glucose-6-phosphatase (Von Gierke disease)
• Type II: Lysosomal α-1,4-glucosidase (Pompe disease)
• Type III: Glycogen debranching enzyme (Cori/Forbes disease)
• Type IV: Branching enzyme (Andersen disease)
• Type V: Muscle glycogen phosphorylase (McArdle disease)
• Type VI: Liver glycogen phosphorylase (Hers disease)
• Type VII: Muscle phosphofructokinase (Tarui disease)
• Type VIII: Liver phosphorylase kinase (rare)
• Type IX: Phosphorylase kinase (X-linked)
• Type X–XI: Various rare defects in glycogen metabolism

Glycogen Storage Disease Type I (Von Gierke Disease)

Epidemiology

• Incidence: ~1 in 100,000–200,000 live births.
• Onset: Infancy (3–6 months) with symptoms of fasting intolerance.
• No sex predilection.

Pathophysiology

• Deficiency of glucose-6-phosphatase (G6Pase) in liver and kidney impairs the final step of gluconeogenesis and glycogenolysis.
• Accumulation of glycogen and fat in hepatocytes and renal tubular cells.
• Excess glucose-6-phosphate shunts into glycolysis and lipogenesis, causing lactic acidosis, hyperlipidemia, and hyperuricemia.

Clinical Presentation

• Severe fasting hypoglycemia: irritability, seizures, coma.
• Lactic acidosis and elevated ketones.
• Hepatomegaly and renomegaly (palpable masses).
• Growth retardation; “doll-like” cherubic facies with fatty cheeks.
• Hyperuricemia: risk of gout.
• Hypertriglyceridemia.

Diagnostic Evaluation

• Laboratory:
• Blood glucose: low (<40 mg/dL).
• Lactate and uric acid: elevated.
• Triglycerides and cholesterol: elevated.
• 24-hour urine uric acid excretion: increased.
• Liver biopsy: marked glycogen accumulation with minimal inflammation.
• Molecular genetic testing: confirm G6PC gene mutations.

Management

1. Maintain normoglycemia:
2. Frequent oral feeds rich in complex carbohydrates.
3. Uncooked cornstarch every 4–6 hours as slow-release glucose source.
4. Continuous nocturnal gastric drip feed in severe cases.
5. Treat metabolic complications:
6. Allopurinol for hyperuricemia.
7. Lipid-lowering agents for hypertriglyceridemia.
8. Monitor growth, liver function, renal function, and for hepatic adenomas.
9. Liver transplantation may be indicated for refractory disease or complications.

Nursing Considerations

• Monitor blood glucose and lactate levels regularly.
• Maintain strict feeding schedules; educate caregivers on cornstarch dosing.
• Assess for signs of hypoglycemia (sweating, irritability, tremors).
• Support growth and developmental milestones; coordinate multidisciplinary care.
• Provide dietary counseling and reinforce adherence.

Prognosis

• Improved survival with early diagnosis and strict metabolic control.
• Risk of hepatic adenomas and renal disease persists; regular screening required.
• Neurodevelopmental outcomes generally favorable when hypoglycemia is prevented.

Patient Education and Lifestyle Modifications

• Emphasize importance of routine cornstarch therapy and planned meals/snacks.
• Avoid prolonged fasting; carry glucose sources for emergencies.
• Encourage compliance with medications (allopurinol, lipid-lowering agents).
• Genetic counseling for the patient and family; sibling testing recommended.

References

1. Wolfsdorf JI, Weinstein DA. Glycogen storage diseases. Rev Endocr Metab Disord. 2003;4(1):95–102.
2. Kishnani PS, Austin SL, Arn P, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014;16(11):e1.
3. Lee PJ, Weinstein DA. Glycogen storage disease type I: diagnosis and treatment update. Curr Treat Options Gastroenterol. 2017;15(3):428–443.