How do you approach diagnosis and treatment of inborn errors of metabolism?

Inborn errors of metabolism (IEM) diagnosis combines clinical presentation with biochemical and genetic testing. Diagnostic approaches: newborn screening (tandem MS for amino acids, acylcarnitines), specific metabolite measurement (organic acids, mucopolysaccharides), enzyme assays in fibroblasts or leukocytes, and genetic sequencing (panels, exome, genome). Classification includes: amino acid disorders (PKU, maple syrup urine disease), organic acidemias, urea cycle disorders, carbohydrate disorders (galactosemia), lysosomal storage diseases, mitochondrial disorders, and fatty acid oxidation defects. Treatment strategies: dietary restriction (limit toxic precursor), supplementation (replace deficient product), cofactor therapy (vitamin-responsive variants), enzyme replacement therapy (lysosomal diseases), substrate reduction therapy, and organ transplant (liver for urea cycle). Gene therapy is emerging for several conditions.