🔑 Key Learning
- GSDs are a group of inherited metabolic disorders affecting glycogen synthesis or breakdown.
- Common clinical themes: hepatomegaly, hypoglycaemia, muscle weakness, lactic acidosis.
- Diagnosis is based on clinical features, biochemical testing, and enzyme/genetic analysis.
- Management includes strict dietary control and, in some cases, enzyme replacement or organ transplantation.
- McArdle (GSD V): Adolescent with exercise-induced cramps and “second wind”
🧬 Overview
Glycogen storage diseases (GSDs) are caused by deficiencies in enzymes required for glycogen metabolism. This leads to abnormal accumulation or structure of glycogen in tissues such as the liver, muscle, and heart.
General Management Principles:
- Nasogastric glucose infusion (in children <2 yrs) to prevent hypoglycaemia
- Frequent small carbohydrate meals
- Uncooked cornstarch as a slow-release glucose source
- Allopurinol (for hyperuricaemia in GSD I)
- Avoidance of fasting
🍬 GSD I – Von Gierke Disease
🧬 Pathophysiology
- Deficiency: Glucose-6-phosphatase (Type Ia) or glucose-6-phosphate translocase (Type Ib)
- Impaired gluconeogenesis and glycogenolysis → severe hypoglycaemia
👀 Clinical Features
- Severe fasting hypoglycaemia
- Hepatomegaly
- Lactic acidosis
- Hyperuricaemia and hyperlipidaemia
💊 Management
- Avoid fasting
- Regular meals with slow-release glucose (uncooked cornstarch)
- Allopurinol (↓ uric acid), lipid-lowering therapy
❤️ GSD II – Pompe Disease
🧬 Pathophysiology
- Deficiency: Acid alpha-glucosidase (GAA) → glycogen accumulation in lysosomes
👀 Clinical Features
- Cardiomegaly, heart failure
- Proximal muscle weakness (incl. respiratory)
- Motor delay
💊 Management
- Enzyme replacement therapy (alglucosidase alfa)
- Supportive cardiopulmonary care
🧱 GSD III – Cori (Forbes) Disease
🧬 Pathophysiology
- Deficiency: Glycogen debranching enzyme
- Accumulation of abnormally structured glycogen
👀 Clinical Features
- Hepatomegaly
- Mild hypoglycaemia
- Muscle weakness (onset in adolescence)
💊 Management
- High-protein diet
- Frequent meals with cornstarch
- Avoid fasting
🧬 GSD IV – Andersen Disease
🧬 Pathophysiology
- Deficiency: Glycogen branching enzyme → formation of amylopectin-like, insoluble glycogen
👀 Clinical Features
- Hepatomegaly
- Failure to thrive
- Progressive cirrhosis → liver failure
💊 Management
- Liver transplantation often required
- Supportive care for liver failure
🏃♂️ GSD V – McArdle Disease
🧬 Pathophysiology
- Deficiency: Muscle glycogen phosphorylase → impaired energy during exercise
👀 Clinical Features
- Exercise intolerance, cramps
- "Second wind" phenomenon
- Myoglobinuria
💊 Management
- Avoid strenuous exercise
- Carbohydrate supplementation before activity
- High-protein diet and aerobic conditioning
🍗 GSD VI – Hers Disease
🧬 Pathophysiology
- Deficiency: Liver glycogen phosphorylase
👀 Clinical Features
- Mild hypoglycaemia
- Hepatomegaly
- Growth delay
💊 Management
- Frequent meals with slow-release carbohydrates
- Generally mild; supportive care
🏋️♂️ GSD VII – Tarui Disease
🧬 Pathophysiology
- Deficiency: Phosphofructokinase (PFK) in skeletal muscle
👀 Clinical Features
- Exercise intolerance
- Myoglobinuria
- Haemolysis in some patients
💊 Management
- Avoid anaerobic activity
- High-protein diet
- Manage rhabdomyolysis complications
🧬 GSD IX – Phosphorylase Kinase Deficiency
🧬 Pathophysiology
- Deficiency in phosphorylase kinase → primarily affects liver
👀 Clinical Features
- Hepatomegaly
- Mild fasting hypoglycaemia
- Growth delay
💊 Management
- High-carbohydrate diet with frequent feeds
- Generally mild; supportive treatment only
📝 Exam Clues & Clinchers
- McArdle (GSD V): Adolescent with exercise-induced cramps and “second wind”
- Von Gierke (GSD I): Infant with severe fasting hypoglycaemia, hepatomegaly, hyperlipidaemia
- Pompe (GSD II): Infant with floppy tone, cardiomegaly, respiratory distress
- Cori (GSD III): Child with mild hypoglycaemia and hepatomegaly + myopathy
- Andersen (GSD IV): Infant with hepatomegaly and signs of progressive liver disease