title: Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated membrane protein LAMP-1 as a diagnostic marker.
abstract: 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 micrograms/L with the 5th and 95th percentile at 175 and 448 micrograms/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.
authors.affiliation: Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia. omeikle@medicine.adelaide.edu.au
authors.forename: P J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: D A
authors.initials: DA
authors.lastname: Brooks
authors.forename: E M
authors.initials: EM
authors.lastname: Ravenscroft
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: R E
authors.initials: RE
authors.lastname: Williams
authors.forename: A E
authors.initials: AE
authors.lastname: Jaunzems
authors.forename: T K
authors.initials: TK
authors.lastname: Chataway
authors.forename: L E
authors.initials: LE
authors.lastname: Karageorgos
authors.forename: R C
authors.initials: RC
authors.lastname: Davey
authors.forename: C D
authors.initials: CD
authors.lastname: Boulter
authors.forename: S R
authors.initials: SR
authors.lastname: Carlsson
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts; D015200:Fluoroimmunoassay; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016464:Lysosomal Storage Diseases / Q000175:diagnosis*; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000737:chemistry / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000097:blood*; D008854:Microscopy, Electron; D008875:Middle Aged
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins