Вступ до спадкових порушень обміну речовин

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

• 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.

Inherited metabolic disorders are typically grouped by the affected substrate, for example:

• Amino acid metabolism disorders

• Carbohydrate metabolism disorders

• Fatty acid metabolism disorders

• Purine and pyrimidine metabolism disorders

All states in the United 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 algorithms.

Metabolic defects that primarily cause disease in adults (eg, gout, porphyria), are organ-specific (eg, Wilson disease, congenital adrenal hyperplasia), or are common (eg, cystic fibrosis, hemochromatosis) are discussed elsewhere in THE MANUAL. For inherited disorders of lipoprotein metabolism, see table Genetic (Primary) Dyslipidemias.