Laboratory analysis of amino acids, 2018 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Amino acid abnormalities are observed in a broad spectrum of inherited metabolic diseases, such as disorders of amino acid metabolism and transport, organic acidemias, and ureagenesis defects. Comprehensive analysis of physiologic amino acids in blood, urine, and cerebrospinal fluid is typically performed in the following clinical settings: evaluation of symptomatic patients in whom a diagnosis is not known; evaluation of previously diagnosed patients to monitor treatment efficacy; evaluation of asymptomatic or presymptomatic (at-risk) relatives of known patients; follow-up testing for an abnormal newborn screen; and assessment of dietary protein adequacy or renal function in general patient populations. Currently, the most common analytical method to quantify amino acids is based on ion exchange chromatography using post-column derivatization with ninhydrin and spectrophotometric detection. Newer methodologies are based on liquid chromatographic separation with detection by mass spectrometry or spectrophotometry. Amino acid analysis by nonseparation methods, such as the flow injection–tandem mass spectrometric (MS/MS) method used for newborn screening, is considered inadequate for the diagnosis of at-risk patients. The purpose of this document is to provide a technical standard for amino acid analysis as applied to the diagnosis and management of inborn errors of metabolism.