A 3-year-old boy from Delhi presents with severe hypoglycemia (blood glucose 35 mg/dL) and hepatomegaly during a routine clinic visit. His mother reports he becomes irritable and sweaty if meals are delayed by 2–3 hours. Physical examination reveals a protuberant abdomen with a firm, enlarged liver extending 8 cm below the costal margin. Serum lactate is elevated at 6 mmol/L (normal <2). Liver biopsy shows 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 (Von Gierke disease) is caused by deficiency of glucose-6-phosphatase, the final enzyme in both gluconeogenesis and glycogenolysis. This leads to severe fasting hypoglycemia within 3–4 hours of the last meal. ### Pathognomonic Features in This Case | Feature | GSD Type I | Clinical Finding | |---------|-----------|------------------| | **Fasting hypoglycemia** | Severe, within 3–4 hours | ✓ Present (irritability, sweating) | | **Hepatomegaly** | Massive (up to 3–4× normal) | ✓ Liver 8 cm below costal margin | | **Lactic acidosis** | Marked elevation | ✓ Lactate 6 mmol/L | | **Glycogen structure** | Normal (α-1,4 and α-1,6 bonds intact) | ✓ Biopsy shows normal structure | | **Age of onset** | Infancy to early childhood | ✓ 3 years old | ### Biochemical Mechanism 1. Glucose-6-phosphatase deficiency blocks the final step of glucose production 2. Glucose-6-phosphate accumulates and is shunted into: - Glycogen synthesis → hepatomegaly - Lactate production → lactic acidosis - Fatty acid synthesis → hyperlipidemia 3. Severe hypoglycemia results because the liver cannot release free glucose into the bloodstream **High-Yield:** The combination of **severe fasting hypoglycemia + massive hepatomegaly + lactic acidosis + normal glycogen structure** is pathognomonic for GSD Type I. ### Clinical Pearl Von Gierke disease patients require frequent feeds (every 2–3 hours) or continuous nasogastric feeding at night to prevent hypoglycemia. Uncooked cornstarch is used as a slow-release glucose source. ### Differential Exclusion - **Type II (Pompe):** Acid maltase deficiency → muscle weakness, cardiomegaly, infantile form fatal by age 2; this child is 3 and has no muscle involvement - **Type III (Cori):** Debranching enzyme deficiency → hepatomegaly but hypoglycemia is milder and occurs after 4–5 hours; lactic acidosis less severe - **Type IV (Andersen):** Branching enzyme deficiency → cirrhosis, hepatic failure by age 5; glycogen has abnormal structure (limit dextrin-like) [cite:Robbins 10e Ch 7]