Treatment and Management of Metabolic Disorders
Principles of management
Management follows directly from pathophysiology: reduce substrate load (dietary restriction of the offending amino acid or protein, avoidance of fasting), increase clearance (hydration, carnitine supplementation, dialysis for severe hyperammonemia), bypass the block (cofactor supplementation such as biotin, thiamine, pyridoxine, riboflavin, or carnitine; alternate pathway drugs such as sodium benzoate/phenylbutyrate for urea cycle defects; sapropterin for BH4-responsive phenylketonuria), and support affected organs (enzyme replacement for selected lysosomal diseases, substrate reduction, hematopoietic stem cell transplantation for selected disorders).
Acute vs. chronic care
Acute decompensation requires a sick-day protocol: stop protein intake temporarily, provide high-energy carbohydrate to suppress catabolism, correct acidosis and electrolytes, treat infection, and escalate to dialysis for refractory hyperammonemia. Chronic care includes growth and developmental monitoring, dietary adherence support, and surveillance for complications (e.g., cardiomyopathy in fatty acid oxidation defects, renal disease in methylmalonic acidemia).
Traps
Questions test whether you know which interventions are urgent versus chronic, and whether a treatment is disease-modifying or supportive. A frequent error is continuing protein restriction during acute illness when the priority is reversing catabolism. Another is assuming enzyme replacement crosses the blood–brain barrier or treats CNS disease.
Worked example
A child with a urea cycle defect presents with ammonia of 400 µmol/L and encephalopathy. Priorities are stopping protein intake, providing intravenous calories, giving nitrogen-scavenging drugs and arginine/citrulline as appropriate, and arranging urgent dialysis if ammonia does not fall promptly.