title: Urinary lipid profiling for the identification of fabry hemizygotes and heterozygotes.
abstract: BACKGROUND
  Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of the lysosomal hydrolase, alpha-galactosidase, for which enzyme replacement therapy is now available. In this study, we aimed to identify Fabry heterozygotes not only for genetic counseling of families but because it is becoming increasingly obvious that many heterozygous (carrier) females are symptomatic and should be considered for treatment.
  
  
  METHODS
  We measured 29 individual lipid species, including ceramide, glucosylceramide, lactosylceramide, and ceramide trihexoside, in urine samples from Fabry hemizygotes and heterozygotes and from control individuals by electrospray ionization tandem mass spectrometry. Individual analyte species and analyte ratios were analyzed for their ability to differentiate the control and patient groups.
  
  
  RESULTS
  The Fabry hemizygotes had increased concentrations of the substrate for the deficient enzyme, ceramide trihexoside, as well as lactosylceramide and ceramide, along with decreased concentrations of both glucosylceramide and sphingomyelin. Ratios of these analytes improved differentiation between the control and Fabry groups, with the Fabry heterozygotes generally falling between the Fabry hemizygotes and the control group.
  
  
  CONCLUSIONS
  These lipid profiles hold particular promise for the identification of Fabry individuals, may aid in the prediction of phenotype, and are potentially useful for the monitoring of therapy in patients receiving enzyme replacement.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia. maria.fuller@adelaide.edu.au
authors.forename: Maria
authors.initials: M
authors.lastname: Fuller
authors.forename: Peter C
authors.initials: PC
authors.lastname: Sharp
authors.forename: Tina
authors.initials: T
authors.lastname: Rozaklis
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Whitfield
authors.forename: David
authors.initials: D
authors.lastname: Blacklock
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000795:Fabry Disease / Q000235:genetics* / Q000652:urine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008055:Lipids / Q000652:urine*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008055:Lipids