Evaluation of the lysosome-associated membrane protein LAMP-2 as a marker for lysosomal storage disorders

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 44; no. 10; pp. 2094 - 2102
• Main Authors: Hua, Chi T, Hopwood, John J, Carlsson, Sven R, Harris, Ray J, Meikle, Peter J
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.10.1998; American Association for Clinical Chemistry
• Subjects: Adolescent; Adult; Aged; Antigens, CD - blood; Australia; Biological and medical sciences; Biomarkers - blood; Blood Specimen Collection; Child; Child, Preschool; Electrophoresis, Polyacrylamide Gel; Errors of metabolism; Humans; Immunoassay; Infant; Infant, Newborn; Lipids (lysosomal enzyme disorders, storage diseases); Lysosomal Membrane Proteins; Lysosomal Storage Diseases - blood; Lysosomes - metabolism; Medical sciences; Membrane Glycoproteins - blood; Metabolic diseases; Middle Aged; Reference Values; Australia; Performance evaluation; Human; Biological marker; Membrane protein; Lysosome-associated membrane protein; Lysosomal storage disease
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/44.10.2094

For many lysosomal storage disorders, presymptomatic detection, before the onset of irreversible pathology, will greatly improve the efficacy of current and proposed therapies. In the absence of a family history, presymptomatic detection can be achieved only by a comprehensive newborn screening program. Recently we reported that the lysosome-associated membrane protein LAMP-1 was increased in the plasma from approximately 70% of individuals with lysosomal storage disorders. Here we report on the evaluation of a second lysosome-associated membrane protein, LAMP-2, as a marker for this group of disorders. The median concentration of LAMP-2 in the plasma of healthy individuals was 1.21 mg/L, fourfold higher than the median LAMP-1 concentration (0.31 mg/L). LAMP-2 was increased in >66% of patients with lysosomal storage disorders, and the increases coincided with increased LAMP-1 concentrations. The reference intervals for LAMP-1 and LAMP-2 in blood spots taken from newborns were 0.20-0.54 mg/L (n = 1600) and 0.95-3.06 mg/L (n = 1600), respectively. A high correlation was observed between the concentrations of LAMP-1 and LAMP-2 in both control and affected individuals. The higher concentrations of LAMP-2, relative to LAMP-1, in plasma make LAMP-2 an attractive marker; however, the final selection will be dependent on the availability of new diagnostic markers and their ability to detect disorders currently not identified by LAMP-2.