Table III Summary of cases in which the comparative proteomics approach provided informative data

Note that for each case the original diagnosis and its clinical basis are shown. Also indicated are biochemical and/or genetics analyses that validate the final diagnosis. GALC, galactosylceramidase; HEXA, β-hexosaminidase α.

IdentifierDiagnosis (basis)Informative lysosomal protein by comparative MSSupporting dataAllele 1Allele 2
Positive controls (known lysosomal defect)
    UMB 563MPSIIIA (unknown criteria, not genetic)SGSHGeneticSGSH 746G→A (R245H)SGSH 746G→A (R245H)
    HSB 148Pediatric CNS/Tay-Sachs disease (enzyme assay)HEXAEnzyme assay
    UMB 784Classical LINCL (ultrastructural pathology)TPP1Enzyme assay, geneticTPP1 3556G→C (splicing defect)TPP1 3556G→C (splicing defect)
    CABM-BR21Classical LINCL (enzyme assay and genetics analysis)TPP1Enzyme assay, geneticTPP1 3556G→C (splicing defect)TPP1 3670C→T (R208Stop)
    UMB 575Krabbe disease (unknown criteria)GALC
Genetic basis undetermined
    CABM-BR25Undiagnosed NCLTPP1Enzyme assay, geneticTPP1 3016T→A (L104Stop)TPP1 3556G→C (splicing defect)
    HSB 4391Undiagnosed LSDTPP1Enzyme assay, geneticTPP1 deletion T2979TPP1 3084C→T (R127Stop)
    CABM-BR19Adult NCL (ultrastructural pathology)CLN5GeneticCLN5 377G→A (C126Y)CLN5 1121A→G (Y374C)
    HSB 4165Adult NCL (ultrastructural pathology)SGSHGeneticSGSH 904T→C (S298P)SGSH 1075G→A (E355K)