Clinical Management and Treatment of Metabolic Disorders
Clinical Management and Treatment of Metabolic Disorders
This domain tests the acute and chronic management of patients with metabolic disorders. You must know the principles of emergency treatment for metabolic crises: stabilization, stopping protein intake, providing calories (e.g., IV glucose), correcting acidosis and hyperammonemia, and using specific therapies (e.g., sodium benzoate/phenylacetate for urea cycle disorders, carnitine for organic acidemias). Understand dietary management (e.g., low-protein diet, special formulas, supplementation of deficient products), enzyme replacement therapy (e.g., for lysosomal storage diseases), and emerging therapies (e.g., chaperones, substrate reduction).
Traps include failing to recognize the need for immediate treatment before diagnosis, using inappropriate fluids (e.g., lactated Ringer's in lactic acidosis), and missing the importance of avoiding fasting in fatty acid oxidation defects. Also, be aware of iatrogenic complications (e.g., carnitine depletion with valproate, hyperammonemia from valproate). In questions, consider the immediate next step in management, which is often stabilization and diagnostic testing in parallel.
A worked example: a child with propionic acidemia presents with vomiting, lethargy, and metabolic acidosis. Management includes stopping protein, providing IV glucose and carnitine, correcting acidosis, and considering dialysis if hyperammonemia is severe. Long-term: low-protein diet, carnitine supplementation, and monitoring for complications (e.g., cardiomyopathy, pancreatitis).
Key Points
- Acute management: stop protein, provide calories (IV glucose), correct acidosis/electrolytes, use specific antidotes.
- Urea cycle disorders: sodium benzoate and phenylacetate for nitrogen scavenging; arginine/citrulline supplementation.
- Organic acidemias: carnitine to enhance excretion of toxic metabolites; biotin for holocarboxylase synthetase deficiency.
- Fatty acid oxidation defects: avoid fasting, provide medium-chain triglycerides (MCTs) for long-chain defects.
- Lysosomal storage diseases: enzyme replacement therapy for some (e.g., Gaucher, Fabry), substrate reduction, hematopoietic stem cell transplant for selected disorders.