Makindo Medical Notes

🧬 Pompe disease is a rare lysosomal storage disorder where glycogen builds up inside lysosomes, damaging the 💓 heart, 🧠 muscles, and 🫁 other organs.

📖 About

• ⚖️ Autosomal recessive inheritance.
• 🦴 Classified as both a metabolic myopathy and a lysosomal storage disorder.
• 👶 Often presents in infancy, but 🧑‍🦳 late-onset forms may manifest in adults.

🔬 Mechanism

A deficiency in acid alpha-glucosidase (acid maltase) prevents the breakdown of glycogen into glucose. As glycogen accumulates inside lysosomes, cells become swollen and damaged, particularly in skeletal muscle, cardiac tissue, and the liver.

🧾 Aetiology

• 🔑 Caused by mutations in the GAA gene.
• ❌ Deficient acid alpha-1,4-glucosidase → glycogen trapped in lysosomes.
• 🔄 Normally, this enzyme converts glycogen → glucose; without it, toxic build-up occurs.

🩺 Clinical Features

• Infantile-onset: 🍼 Hypotonia (“floppy baby”), bulky muscles, and 👅 macroglossia.
• 💓 Massive cardiomegaly → early congestive heart failure.
• 🫀 Hepatomegaly but notably ❌ no ketosis or hypoglycaemia (unlike other metabolic disorders).
• Late-onset: Progressive muscle weakness and respiratory difficulties, often without cardiomegaly.

🔍 Differential Diagnosis

• Duchenne Muscular Dystrophy: Similar progressive weakness, but X-linked and due to dystrophin deficiency.
• Other glycogen storage diseases: e.g., Cori or McArdle disease, which present differently (hypoglycaemia, exercise intolerance).

🧪 Investigations

• 🧾 CK Levels: May be normal or mildly elevated.
• 🖥️ Abdominal Ultrasound: Hepatomegaly.
• 💓 Echocardiography: Hypertrophic cardiomyopathy/cardiomegaly.
• 🧪 LFTs: Raised AST and LDH.
• 🧬 Muscle Biopsy: Glycogen-filled lysosomes, vacuolisation.
• 🔬 Electron Microscopy: Confirms glycogen accumulation.
• 💉 Enzyme assay: Low acid alpha-glucosidase confirms diagnosis.
• 🧬 Genetic testing: Identifies GAA gene mutations, useful for family counselling.

💊 Management

• 🚨 Severe infantile forms → often fatal by 6–24 months if untreated.
• ⏳ Late-onset forms → slower progression, survival into adulthood possible.
• 💉 Enzyme replacement therapy (ERT): Recombinant human alpha-glucosidase improves survival, motor function, and cardiac outcomes.
• 🤝 Supportive care: physiotherapy, respiratory support, and cardiac management remain essential.