Biomarker testing for lysosomal diseases: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Measurement of lysosomal disease (LD) biomarkers can reveal valuable information about disease status. Lyso-globotriaosylceramide (lyso-Gb₃), glucosylsphingosine (lyso-Gb₁), galactosylsphingosine (psychosine), and glucose tetrasaccharide (Glca1-6Glca1-4Glca1-4Glc, Glc₄) are biomarkers associated with Fabry, Gaucher, Krabbe, and Pompe disease, respectively. Clinical biomarker testing is performed to guide patient management, including monitoring disease progression and initiating treatment, and in diagnostic evaluations of either symptomatic patients or asymptomatic individuals with a positive family history or abnormal newborn screen. Biomarker analysis can be performed through independent analysis of a single analyte or as a multiplex assay measuring analytes for more than one disorder utilizing liquid chromatographic separation and tandem mass spectrometric detection. These guidelines were developed to provide technical standards for biomarker analysis, results interpretation, and results reporting, highlighting Fabry, Gaucher, Krabbe, and Pompe diseases as examples.