Which glycogen storage disorder is the most common cause of hepatomegaly and hypoglycemia presenting in infancy?

Explanation

## Most Common Glycogen Storage Disorder with Hepatomegaly and Hypoglycemia **Key Point:** Type I glycogen storage disease (von Gierke disease) is the most common GSD presenting with severe fasting hypoglycemia and massive hepatomegaly in infants. ### Pathophysiology Type I GSD results from deficiency of **glucose-6-phosphatase**, the final enzyme in both gluconeogenesis and glycogenolysis. This prevents the conversion of glucose-6-phosphate to free glucose, causing: 1. Severe fasting hypoglycemia (within 3–4 hours of fasting) 2. Massive hepatomegaly (up to 2–3× normal size) 3. Lactic acidosis and hyperuricemia ### Clinical Presentation - **Age of onset:** 3–4 months (when feeding intervals lengthen) - **Hepatomegaly:** Marked, with smooth edge - **Hypoglycemia:** Severe, symptomatic (seizures, loss of consciousness) - **Growth:** Doll-like face, short stature - **Metabolic:** Lactic acidosis, hyperuricemia (gout risk), hyperlipidemia ### Comparison with Other Types | Feature | Type I | Type II | Type III | Type IV | |---------|--------|---------|----------|----------| | **Enzyme defect** | Glucose-6-phosphatase | Acid maltase | Debranching enzyme | Branching enzyme | | **Hepatomegaly** | Massive | Absent/mild | Moderate | Progressive | | **Hypoglycemia** | Severe, early | No | Mild | No | | **Muscle involvement** | No | Severe (infantile form) | Mild | No | | **Presentation** | 3–4 months | Infancy (infantile) or childhood | 6–12 months | 6–12 months | | **Prognosis** | Good with management | Poor (infantile form) | Good | Cirrhosis risk | **High-Yield:** Type I is the most common GSD overall (~25% of all GSDs) and the most common cause of severe fasting hypoglycemia in infants. ### Management - Frequent feeds or continuous nasogastric feeding - Uncooked cornstarch (provides sustained glucose release) - Allopurinol (for hyperuricemia) - Strict carbohydrate management **Clinical Pearl:** The "doll-like" facies (round face, full cheeks) and short stature are characteristic clinical signs that should prompt suspicion of Type I GSD.