Disorders of Metabolism
This domain covers inborn errors and acquired metabolic disease. Know the major categories: carbohydrate disorders (diabetes, glycogen storage diseases, galactosemia), amino acidopathies (phenylketonuria, maple syrup urine disease, homocystinuria), organic acidemias, fatty acid oxidation defects, and lysosomal storage diseases. Newborn screening detects many of these; confirmatory testing follows abnormal screens.
Diabetes: understand diagnostic criteria (fasting glucose ≥126 mg/dL, 2-hour OGTT ≥200, HbA1c ≥6.5%, random ≥200 with symptoms), and the limitations of HbA1c in hemoglobinopathies and altered red cell turnover. Know hypoglycemia causes and the role of C-peptide and insulin in distinguishing endogenous from exogenous hyperinsulinism.
Lipid disorders: Fredrickson classification, familial hypercholesterolemia, and the significance of triglycerides >500 mg/dL for pancreatitis risk. Uric acid disorders, porphyrias, and disorders of metal metabolism (Wilson disease, hemochromatosis) appear in questions.
Worked example: a newborn with elevated phenylalanine on screening and a phenylalanine-to-tyrosine ratio >3 suggests PKU; confirm with quantitative amino acids and initiate dietary therapy promptly.
Trap: attributing abnormal newborn screening results to disease without confirmatory testing-prematurity and parenteral nutrition alter many analytes.