title: Immunoquantification of alpha-galactosidase: evaluation for the diagnosis of Fabry disease.
abstract: BACKGROUND
  Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from a deficiency of the lysosomal exoglycohydrolase, alpha-galactosidase. Enzyme replacement therapy is currently available for Fabry disease, but early diagnosis before the onset of irreversible pathology will be mandatory for successful treatment. Presymptomatic detection would be possible through the use of a newborn-screening program. We report on the use of sensitive assays for the measurement of alpha-galactosidase protein and activity and for the protein saposin C, which are diagnostic markers for Fabry disease.
  
  
  METHODS
  Two sensitive immunoassays for the measurement of alpha-galactosidase activity and protein were used to determine the concentrations of alpha-galactosidase in dried filter-paper blood spots and plasma samples from control patients and patients with a lysosomal storage disorder (LSD).
  
  
  RESULTS
  Fabry hemizygous individuals were clearly identified from control populations by decreases in both alpha-galactosidase activity and protein. Fabry heterozygotes generally fell between the hemizygotes and controls. Including the measurement of saposin C enabled differentiation between Fabry heterozygotes and controls. In blood spots, all Fabry individuals could be distinguished from control blood spots as well as from 16 other LSD patients.
  
  
  CONCLUSIONS
  The determination of alpha-galactosidase activity or protein in dried filter-paper blood spots could be used for the diagnosis of Fabry patients. With further validation, these assays could be used for the identification of Fabry patients in newborn-screening programs and may also be suitable for screening high-risk populations.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA, Australia. maria.fuller@adelaide.edu.au
authors.forename: Maria
authors.initials: M
authors.lastname: Fuller
authors.forename: Melanie
authors.initials: M
authors.lastname: Lovejoy
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Harkin
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000328:Adult; D001800:Blood Specimen Collection; D004796:Clinical Enzyme Tests; D000795:Fabry Disease / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D049231:Saposins / Q000097:blood; D012680:Sensitivity and Specificity; D000519:alpha-Galactosidase / Q000097:blood*
chemical_list: D049231:Saposins; D000519:alpha-Galactosidase