## Glycogen Storage Disease Type I (Von Gierke Disease) **Key Point:** GSD Type I is caused by deficiency of **glucose-6-phosphatase**, the enzyme responsible for the final step of both gluconeogenesis and glycogenolysis — conversion of glucose-6-phosphate to free glucose in the liver. ### Pathophysiology Glucose-6-phosphatase catalyzes the terminal reaction in glucose production: $$\text{Glucose-6-phosphate} \xrightarrow{\text{G6Pase}} \text{Glucose} + \text{Pi}$$ Without this enzyme: - Glucose cannot be released from the liver into the bloodstream - Severe **fasting hypoglycemia** develops within 3–4 hours of fasting - Glucose-6-phosphate accumulates and is shunted into glycolysis and lipogenesis ### Clinical Features - Severe hypoglycemia (blood glucose < 40 mg/dL during fasting) - Hepatomegaly (massive — liver can be 2–3× normal size) - "Doll-like" facies with fat cheeks and thin extremities - Growth retardation - Lactic acidosis and hyperuricemia (leading to gout in childhood) - Bleeding tendency (platelet dysfunction) ### Biochemical Findings - **Fasting glucose:** < 40 mg/dL - **Lactate:** markedly elevated (2–5 mmol/L) - **Uric acid:** elevated (risk of gout) - **Triglycerides:** severely elevated (lipemic plasma) **High-Yield:** GSD Type I is the most severe form and the only one with profound fasting hypoglycemia. Diagnosis is confirmed by **enzyme assay** (glucose-6-phosphatase activity in liver biopsy) or **genetic testing**. **Clinical Pearl:** Management requires frequent feeding (every 2–3 hours) or continuous nasogastric infusion of glucose polymers at night to prevent hypoglycemia.
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