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

Abstract

Amino acid abnormalities are observed in a broad spectrum of inheritedmetabolic diseases, such as disorders of amino acid metabolism and transport,organic acidemias, and ureagenesis defects. Comprehensive analysis of physiologicamino acids in blood, urine, and cerebrospinal fluid is typically performed in thefollowing clinical settings: evaluation of symptomatic patients in whom a diagnosisis not known; evaluation of previously diagnosed patients to monitor treatmentefficacy; evaluation of asymptomatic or presymptomatic (at-risk) relatives of knownpatients; follow-up testing for an abnormal newborn screen; and assessment ofdietary protein adequacy or renal function in general patient populations.Currently, the most common analytical method to quantify amino acids is based on ionexchange chromatography using post-column derivatization with ninhydrin andspectrophotometric detection. Newer methodologies are based on liquidchromatographic separation with detection by mass spectrometry or spectrophotometry.Amino acid analysis by nonseparation methods, such as the flow injection–tandem massspectrometric (MS/MS) method used for newborn screening, is considered inadequatefor the diagnosis of at-risk patients. The purpose of this document is to provide atechnical standard for amino acid analysis as applied to the diagnosis andmanagement of inborn errors of metabolism.