A 3-year-old boy from rural Uttar Pradesh presents with severe hypoglycaemia (blood glucose 35 mg/dL) and hepatomegaly during a 4-hour fast. His parents report failure to thrive, developmental delay, and recurrent episodes of seizures triggered by fasting. On examination, he has a doll-like face, short stature, and a markedly enlarged liver. Blood lactate is elevated at 8 mmol/L (normal <2). Liver biopsy shows excessive glycogen accumulation with normal structure. Which glycogen storage disorder is most likely?

Explanation

## Diagnosis: Glycogen Storage Disease Type I (Von Gierke Disease) ### Clinical Presentation Match **Key Point:** GSD Type I is caused by deficiency of **glucose-6-phosphatase**, the final enzyme in both glycogenolysis and gluconeogenesis. This blocks the final step of glucose release into the bloodstream. ### Pathognomonic Features Present in This Case | Feature | GSD Type I | Clinical Finding | |---------|-----------|------------------| | **Hypoglycaemia** | Severe, fasting-triggered | Present (35 mg/dL after 4 hours) | | **Hepatomegaly** | Marked (up to 2–3× normal) | Present | | **Lactic acidosis** | Characteristic | Elevated lactate (8 mmol/L) | | **Doll-like facies** | Classic appearance | Noted on exam | | **Age of onset** | Infancy to early childhood | 3 years old | | **Glycogen structure** | Normal (Type I) | Confirmed on biopsy | | **Seizures** | From severe hypoglycaemia | Recurrent, fasting-triggered | ### Biochemical Mechanism 1. Glucose-6-phosphatase deficiency blocks the final step of both glycogenolysis and gluconeogenesis 2. Glucose-6-phosphate accumulates → shunted to: - Glycogen synthesis → hepatomegaly - Glycolysis → lactate production (lactic acidosis) - Pentose phosphate pathway → hyperuricaemia (gout risk) 3. No glucose released → severe hypoglycaemia on fasting **High-Yield:** GSD Type I is the **most severe** glycogen storage disorder in terms of hypoglycaemic episodes and metabolic derangement. ### Why This Is Type I and Not Type III **Clinical Pearl:** Although both GSD I and III present with hepatomegaly and hypoglycaemia, the **severity and lactate elevation** are hallmarks of Type I. GSD III (debrancher deficiency) causes milder hypoglycaemia and does not produce significant lactic acidosis. ### Management Implications - Frequent feeds (every 2–3 hours) or continuous nasogastric feeding - Uncooked cornstarch (provides slow glucose release) - Avoid fasting - Monitor for complications: gout, kidney disease, hepatic adenomas **Mnemonic:** **GALANT** = **G**lucose-6-phosphatase deficiency, **A**cidosis (lactic), **L**arge liver, **A**cute hypoglycaemia, **N**ormal glycogen structure, **T**ype I