title: Residual enzymatic activity as a prognostic factor in patients with Gaucher disease type 1: correlation with Zimran and GAUSS-I index and the severity of bone disease.
abstract: BACKGROUND
  Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited.
  
  
  METHODS
  We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A > C (T134P), 1%; c.721G > A (G202R), 17%; c.1090G > T (G325W), 13.9%; c.1208G > A (S364N), 4.1%; c.1226A > G (N370S), 17.8%; c.1246G > A (G377S), 17.6%; c.1289C > T (P391L), 8.5%; c.1448T > C (L444P), 3%; and c.1504C > T (R463C), 24.5%. Recombinant alleles, deletion of 55 bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity.
  
  
  RESULTS
  The ERA showed a statistically significant correlation with chitotriosidase (P < 0.001), age (P < 0.001), spleen size (P < 0.001), 'Zimran's Severity Score Index' (P < 0.01) and the 'Gaucher Disease Severity Score Index-Type I' (P <  0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship (P < 0.01) between the two variables.
  
  
  CONCLUSIONS
  This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA.
authors.affiliation: From the Department of Internal Medicine, "Lozano Blesa" University Hospital, Zaragoza, Spain, mantorralba@gmail.com.
authors.forename: M A
authors.initials: MA
authors.lastname: Torralba
authors.affiliation: From the Department of Internal Medicine, "Lozano Blesa" University Hospital, Zaragoza, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Olivera
authors.affiliation: Department of Internal Medicine, "Infanta Cristina" University Hospital, Badajoz, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Bureo
authors.affiliation: Department of Pediatrics, "La Fé" University Hospital, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: Department of Hematology, "Virgen Del Rocío" University Hospital, Sevilla, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Nuñez
authors.affiliation: Department of Hematology, "Dr Peset" University Hospital, Valencia, Spain and.
authors.forename: P
authors.initials: P
authors.lastname: León
authors.affiliation: Department of Hematology, "Ramón Y Cajal" University Hospital, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Villarrubia
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015519:Bone Density; D001847:Bone Diseases / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D020440:Gene Duplication; D005820:Genetic Testing; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008159:Lumbar Vertebrae / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D017384:Sequence Deletion; D012720:Severity of Illness Index; D013030:Spain; D013154:Spleen / Q000201:enzymology*; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase