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Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated membrane protein LAMP-1 as a diagnostic marker

¹ Lysosomal Diseases Research Unit, Departments of Chemical Pathology and Histopathology, Women's and Children's Hospital, 72 King William Rd., North Adelaide, South Australia, 5006, Australia.

² Department of Medical Biochemistry and Biophysics, Umea University, Umea, S-901 87, Sweden.
^a Author for correspondence. Fax 61 8–8204 7100;

Early diagnosis of lysosomal storage disorders (LSDs), before the onset 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 disorders. From studies of both normal and LSD-affected human skin fibroblasts we identified the lysosome-associated membrane protein LAMP-1 as a potential diagnostic marker. We have developed a sensitive method for the quantification of this protein with a time-resolved fluorescence immunoassay. A soluble form of LAMP-1 was observed in plasma samples, and determination of 152 unaffected individuals gave a median value of 303 µg/L with the 5th and 95th percentile at 175 and 448 µg/L respectively. Plasma samples from 320 LSD-affected individuals representing 25 different disorders were assayed. We observed that 17 of the 25 disorder groups tested had >88% of individuals above the 95th percentile 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 suggest that LAMP-1 may be a useful marker in newborn screening for LSDs.

Key Words: indexing terms: blood spot • Guthrie card • skin fibroblast • time-resolved fluorescence immunoassay

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