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Amino acids are the building blocks of proteins and serve as neurotransmitters (glycine, glutamate, γ-aminobutyric acid) or as precursors of hormones, coenzymes, pigments, purines, or pyrimidines. Eight amino acids, referred to as essential (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, valine, threonine, and tryptophan), cannot be synthesized by humans and must be obtained from dietary sources. The others are formed endogenously. Each amino acid has a unique degradative pathway by which its nitrogen and carbon components are used for the synthesis of other amino acids, carbohydrates, and lipids. Disorders of amino acid metabolism and transport (Chap. 414) are individually rare—the incidences range from 1 in 10,000 for cystinuria or phenylketonuria to 1 in 200,000 for homocystinuria or alkaptonuria—but collectively, they affect perhaps 1 in 1000 newborns. Almost all are transmitted as autosomal recessive traits.

The features of inherited disorders of amino acid catabolism are summarized in Table 413-1. In general, these disorders are named for the compound that accumulates to highest concentration in blood (-emias) or urine (-urias). In the aminoacidopathies, the parent amino acid is found in excess, whereas products in the catabolic pathway accumulate in organic acidemias. Which compound(s) accumulates depends on the site of the enzymatic block, the reversibility of the reactions proximal to the lesion, and the availability of alternative pathways of metabolic “runoff.” Biochemical and genetic heterogeneity are common. Five distinct forms of hyperphenylalaninemia, nine forms of homocystinuria, and methylmalonic acidemia are recognized. Such heterogeneity reflects the presence of a large array of molecular defects.

TABLE 413-1Inherited Disorders of Amino Acid Metabolism

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