Introduction to Inherited Disorders of Metabolism
Most inherited disorders of metabolism (also called inborn errors of metabolism) are caused by mutations in genes that code for enzymes; enzyme deficiency or inactivity leads to accumulation of substrate precursors or metabolites or to deficiencies of the enzyme’s products. Hundreds of disorders exist, and although most inherited disorders of metabolism are extremely rare individually, collectively they are not rare. The disorders are typically grouped by the affected substrate (eg, carbohydrates, amino acids, fatty acids).
Most states routinely do neonatal screening of all newborns for specific inherited disorders of metabolism and other conditions, including phenylketonuria, tyrosinemia, biotinidase deficiency, homocystinuria, maple syrup urine disease, and galactosemia. Many states have an expanded screening program that covers many more inherited disorders of metabolism, including disorders of fatty acid oxidation and other organic acidemias. For a comprehensive review of each of these conditions, see also the American College of Medical Genetics and Genomics' (ACMG) newborn screening ACT sheets and algorithm table.
Metabolic defects that primarily cause disease in adults (eg, gout, porphyria), are organ-specific (eg, Wilson disease, congenital adrenal hypoplasia), or are common (eg, cystic fibrosis, hemochromatosis) are discussed elsewhere in The Manual. For inherited disorders of lipoprotein metabolism, see Table: Genetic (Primary) Dyslipidemias.