EVALUATION OF THE LYSOSOME-ASSOCIATED MEMBRANE-PROTEIN LAMP-2 AS A MARKER FOR LYSOSOMAL STORAGE DISORDERS

For many lysosomal storage disorders, presymptomatic detection, before the onset oi: irreversible pathology, will greatly improve the effica cy of current and proposed therapies. In the absence of a family histo ry, presymptomatic detection can be achieved only by a comprehensive n ewborn screening program. Recently we reported that the lysosome-assoc iated membrane protein LAMP-1 was increased in the plasma from similar to 70% of individuals with lysosomal storage disorders. Here we repor t on the evaluation of a second lysosome-associated membrane protein, LAMP-2, as a marker for this group of disorders. The median concentrat ion of LAMP-2 in the plasma of healthy individuals was 1.21 mg/L, four fold higher than the median LAMP-1 concentration (0.31 mg/L). LAMP-2 w as increased in >66% of patients with lysosomal storage disorders, and the increases coincided with increased LAMP-1 concentrations. The ref erence intervals for LAMP-1 and LAMP-2 in blood spots taken from newbo rns were 0.20-0.54 mg/L (n = 1600) and 0.95-3.06 mg/L (n = 1600), resp ectively. A high correlation was observed between the concentrations o f LAMP-1 and LAMP-2 in both control and affected individuals. The high er concentrations of LAMP-2 relative to LAMP-1, in plasma make LAMP-2 an attractive marker; however, the final selection will be dependent o n the availability of new diagnostic markers and their ability to defe ct disorders currently not identified by LAMP-2.