DIAGNOSIS OF LYSOSOMAL STORAGE DISORDERS - EVALUATION OF LYSOSOME-ASSOCIATED MEMBRANE-PROTEIN LAMP-1 AS A DIAGNOSTIC MARKER

Early diagnosis of lysosomal storage disorders (LSDs), before the onse t of irreversible pathologies, will be a key factor in the development of effective therapies for many of these disorders. Newborn screening offers a potential mechanism for the early detection of these disrode rs. From studies of both normal and LSD-affected human skin fibroblast s we identified the lysosome-associated membrane protein LAMP-1 as a p otential diagnostic marker. We have developed a sensitive method for t he quantification of this protein with a time-resolved fluorescence: i mmunoassay. A soluble form of LAMP-1 was observed in plasma samples, a nd determination of 152 unaffected individuals gave a median value of 303 mu g/L with the 5th and 95th percentile at 175 and 448 mu g/L resp ectively. Plasma samples from 320 LSD-affected individuals representin g 25 different disorders were assayed. We observed that 17 of the 25 d isorder groups tested had >88% of individuals above the 95th percentil e of the control population, with 12 groups having 100% above the 95th percentile. Overall, 72% of patients had LAMP-1 concentrations above the 95th percentile of the unpartitioned control population. We sugges t that LAMP-1 may be a useful marker in newborn screening for LSDs.