Fuller, M.Tucker, J.Lang, D.Dean, C.Fietz, M.Meikle, P.Hopwood, J.2011-10-312011-10-312011Journal of Medical Genetics, 2011; 48(6):422-4250022-25931468-6244http://hdl.handle.net/2440/67097Background: Lysosomal protein profiling is being developed as a high throughput method to screen populations for lysosomal storage disorders (LSD). Design: 1415 blood spots from patients referred to a metabolic clinic for LSD were screened using a single multiplex assay for 14 proteins in a dried blood spot. Results: All patients with Pompe disease, metachromatic leukodystrophy, and mucopolysaccharidosis (MPS) type I, IIIA, IIIB and VI were identified by reduced lysosomal protein. Five samples were identified as possible pseudo-arylsulfatase A deficiency; four were confirmed. One multiple sulfatase deficiency patient was identified with multiple reduced sulfatase proteins. There were 10 MPS II patients identified with reduced iduronate 2-sulfatase, and one MPS II patient with iduronate 2-sulfatase in the unaffected range. For Fabry disease, 10 male patients were identified with reduced α-galactosidase and 2/6 female Fabry heterozygotes returned α-galactosidase concentrations in the male Fabry range. All 10 mucolipidosis II/III patients were identified with multiple raised proteins. For 79 blood spots with chitotriosidase >3.4 mg/l, a follow-up one-plex chitotriosidase assay enabled identification of all nine Gaucher patients. Conclusion: This study demonstrates the sensitivity and specificity of this technology to accurately identify 99% of LSD patients, with the exception of one MPS II false negative.enCopyright status unknownHumansLysosomal Storage DiseasesIduronate Sulfatasealpha-GalactosidaseHexosaminidasesGlycosaminoglycansProteinsMass ScreeningImmunochemistrySensitivity and SpecificityGenetic HeterogeneityMutationChildInfant, NewbornAustraliaFemaleMaleClinical Enzyme TestsHigh-Throughput Screening AssaysJournal article002010916510.1136/jmg.2010.0880960002909586000112-s2.0-7995802639329512Fuller, M. [0000-0001-9092-8942]