A 6-year-old boy presents with muscle pain and dark urine after running. Serum creatine kinase is markedly elevated, but fasting glucose and lactate are normal. Which glycogen storage disorder is most likely, and what feature distinguishes it from Type I?

Explanation

## Type V (McArdle Disease) vs. Type I: Clinical Differentiation ### Clinical Presentation Comparison | Feature | Type V (McArdle) | Type I (Von Gierke) | |---------|-----------------|---------------------| | **Enzyme Defect** | Muscle phosphorylase | Glucose-6-phosphatase | | **Trigger** | Exercise / exertion | Fasting | | **Fasting Glucose** | Normal | Severely low | | **Fasting Lactate** | Normal | Markedly elevated | | **Myoglobinuria** | Present (exercise-induced) | Absent | | **Hepatomegaly** | Absent | Severe | | **Lactic Acidosis** | Absent | Present | | **Muscle Involvement** | Acute necrosis on exertion | Spared | ### Key Point: **Type V is the only GSD where exercise triggers acute muscle necrosis with myoglobinuria, while fasting glucose and lactate remain normal.** This is the cardinal discriminator. Type I patients have the opposite: severe fasting hypoglycemia and lactic acidosis but normal muscle function. ### High-Yield: - **Type V (McArdle):** "Second Wind Phenomenon" — patients experience initial cramping, then relief after 10 minutes (due to increased blood glucose from hepatic glycogenolysis and increased fatty acid oxidation). This is pathognomonic. - **Type I (Von Gierke):** "Fasting Hypoglycemia + Lactic Acidosis" — no exercise intolerance. ### Mnemonic: **"McArdle's = Muscle + Exercise"** — muscle phosphorylase deficiency manifests only during exertion. Contrast with Type I, where the defect is hepatic (glucose-6-phosphatase) and manifests at rest (fasting). ### Clinical Pearl: Type V patients often report a "second wind" phenomenon: initial muscle pain and cramping during exercise, followed by relief and ability to continue activity. This reflects the shift from glycolytic to oxidative metabolism (fatty acids and blood glucose uptake). Type I patients have no exercise intolerance but severe hypoglycemia within 3–4 hours of fasting. ### Warning: ~~Type V causes hepatomegaly~~ — Type V has minimal hepatic involvement. The liver is spared because it has normal glucose-6-phosphatase and can perform gluconeogenesis. Hepatomegaly is a feature of Types I, III, IV, and VI, but NOT Type V. [cite:Robbins 10e Ch 5; Harrison 21e Ch 347]