A 6-month-old girl from Bangalore is brought to the emergency department with severe hypoglycaemia (blood glucose 28 mg/dL), hepatomegaly, and lactic acidosis (pH 7.18, lactate 12 mmol/L). Liver function tests show markedly elevated transaminases and hyperuricaemia (uric acid 9.2 mg/dL). Enzyme assay confirms glucose-6-phosphatase deficiency. After immediate IV dextrose and stabilization, what is the most appropriate next step in long-term management?

Explanation

## Diagnosis Recognition **Key Point:** Glucose-6-phosphatase deficiency = **Glycogen Storage Disease Type I (GSD I, von Gierke disease)** — the most severe glycogen storage disorder. ## Pathophysiology of GSD I Glucose-6-phosphatase catalyzes the final step of both gluconeogenesis and glycogenolysis: $$\text{Glucose-6-phosphate} \xrightarrow{\text{G6Pase}} \text{Glucose}$$ Deficiency causes: 1. **Severe fasting hypoglycaemia** (within 3–4 hours of fasting) 2. **Lactic acidosis** — G6P shunted to glycolysis → pyruvate → lactate 3. **Hyperuricaemia** — increased purine degradation from high AMP/ADP turnover 4. **Hepatomegaly** — massive glycogen and fat accumulation 5. **Growth retardation** — chronic metabolic derangement ## Long-Term Management: Tripod Approach **High-Yield:** GSD I requires THREE simultaneous interventions: ### 1. **Dietary Management: Frequent Feeds + Cornstarch** - Feeds every 2–3 hours during day - **Uncooked cornstarch** at bedtime (1.5–2 g/kg) — provides slow glucose release - Prevents fasting hypoglycaemia - Goal: maintain blood glucose > 70 mg/dL at all times ### 2. **Allopurinol for Hyperuricaemia** - Xanthine oxidase inhibitor - Reduces uric acid production - Prevents gout and uric acid nephrolithiasis (common in GSD I) - **Typical dose:** 10 mg/kg/day in divided doses ### 3. **Genetic Counselling** - Autosomal recessive inheritance - Recurrence risk 25% in siblings - Prenatal diagnosis available **Clinical Pearl:** GSD I is the only glycogen storage disorder where **allopurinol is indicated**. Hyperuricaemia is a hallmark and requires prophylaxis. ## Prognosis & Monitoring | Complication | Monitoring | |--------------|------------| | Renal disease | Annual creatinine, urine protein | | Hepatic adenomas | Annual ultrasound (risk increases with age) | | Cirrhosis | Liver synthetic function, platelet count | | Gout | Serum uric acid target < 6 mg/dL | **Mnemonic:** **GLUE** for GSD I: **G**lucose-6-phosphatase, **L**actic acidosis, **U**ric acid ↑, **E**mergency feeds. ## Why Other Options Fail | Option | Why Incorrect | |--------|---------------| | Ursodeoxycholic acid | Used for cholestasis/PBC, not for GSD I metabolic management; does not address hypoglycaemia or hyperuricaemia | | Continuous glucose infusion | Impractical long-term; cornstarch is the standard; IV glucose only for acute hypoglycaemic crises | | Pegvisomant | Growth hormone antagonist; not indicated in GSD I; does not improve metabolic control or prevent complications |