title: Correlation among genotype, phenotype, and biochemical markers in Gaucher disease: implications for the prediction of disease severity.
abstract: Gaucher disease is a lysosomal storage disorder characterized by a deficiency of the enzyme acid beta-glucosidase. The clinical manifestations of Gaucher disease are highly variable, and although certain genotypes are often associated with mild or severe symptoms, a defined correlation between genotype and phenotype does not exist. Identification of biochemical markers characteristic of pathology may be of use in predicting the progression of the disease state. In this study the relationship among genotype, glycolipid substrates, lysosomal proteins, and the clinical manifestations of Gaucher disease has been evaluated. Plasma glycolipids were analyzed using electrospray ionization-tandem mass spectrometry. Lysosomal-associated membrane protein-1 (LAMP-1) and saposin C were determined by immunoquantification. Patients with Gaucher disease were shown to have an increased 16:0-glucosylceramide/16:0-lactosylceramide ratio and elevated concentrations of LAMP-1 and saposin C in plasma. A general relationship was found to exist among the 16:0-glucosylceramide/16:0-lactosylceramide ratio, LAMP-1 and saposin C levels, and patient phenotype, providing a refinement of the genotype-phenotype correlation. These findings have major implications for the diagnosis, prediction of disease severity, and monitoring of therapy in patients with Gaucher disease.
authors.affiliation: Lysosomal Diseases Research Unit, National Referral Laboratory, Adelaide, South Australia 5006, Australia.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Whitfield
authors.forename: Paul
authors.initials: P
authors.lastname: Nelson
authors.forename: Peter C
authors.initials: PC
authors.lastname: Sharp
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Bindloss
authors.forename: Caroline
authors.initials: C
authors.lastname: Dean
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Ravenscroft
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Fong
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fietz
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D005838:Genotype; D005963:Glucosylceramides / Q000097:blood; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007223:Infant; D007790:Lactosylceramides / Q000097:blood; D051907:Lysosomal Membrane Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D049231:Saposins
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D005963:Glucosylceramides; D006023:Glycoproteins; D007790:Lactosylceramides; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D049231:Saposins; C009744:CDw17 antigen