A 6-year-old boy from Delhi presents with severe fasting hypoglycemia, hepatomegaly, lactic acidosis, and hyperuricemia. Enzyme assay confirms glucose-6-phosphatase deficiency. All of the following are true regarding his condition EXCEPT:

Explanation

## Von Gierke Disease (Type I GSD): Clinical Features and Management ### Pathophysiology **Key Point:** Glucose-6-phosphatase deficiency blocks the final step of both glycogenolysis and gluconeogenesis, preventing hepatic glucose release into the bloodstream. This leads to: - Severe fasting hypoglycemia (within 3–4 hours of fasting) - Massive hepatomegaly (due to glycogen accumulation) - Lactic acidosis (shunting of glucose-6-phosphate to lactate) - Hyperuricemia (increased purine degradation from ATP depletion) ### Clinical Features of Type I GSD | Feature | Mechanism | Severity | |---------|-----------|----------| | Fasting hypoglycemia | Blocked glucose release | **Severe** (< 40 mg/dL) | | Hepatomegaly | Glycogen accumulation | Massive (liver 2–3× normal) | | Lactic acidosis | Shunting to lactate pathway | Chronic metabolic acidosis | | Hyperuricemia | ↑ Purine catabolism from AMP depletion | Gout, uric acid stones | | Hyperlipidemia | ↑ Fatty acid synthesis from acetyl-CoA | Eruptive xanthomas | | Growth retardation | Chronic hypoglycemia + metabolic derangement | "Doll-like" facies | | **Muscle weakness** | **NOT a feature** | **Absent** | ### Key Point: **Type I GSD does NOT cause muscle weakness or exercise intolerance.** This is a hepatic disorder with no primary muscle involvement. Muscle symptoms are characteristic of Type V (McArdle disease) and Type VII (phosphofructokinase deficiency). ### Management Principles 1. **Dietary:** Frequent meals (every 2–3 hours), complex carbohydrates, continuous nasogastric feeding at night to prevent hypoglycemia. 2. **Allopurinol:** Reduces uric acid production and prevents gout, uric acid nephropathy, and renal stones. 3. **Monitoring:** Regular assessment of growth, liver function, renal function, and lipid profile. ### Clinical Pearl: **High-Yield:** The triad of Type I GSD is **(1) severe fasting hypoglycemia, (2) hepatomegaly, (3) lactic acidosis + hyperuricemia.** Muscle is spared — no myopathy, no exercise intolerance. ### Mnemonic: **"Type I = Liver disease (hepatomegaly, hypoglycemia, lactic acidosis); Type V = Muscle disease (myalgia, myoglobinuria, exercise intolerance)."**