title: Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).
abstract: BACKGROUND
  GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.
  
  
  METHODS
  We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1.
  
  
  RESULTS
  
  
  
  METHODS
  N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.
  
  
  CONCLUSIONS
  DS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.
authors.affiliation: University Research Foundation for Lysosomal Storage Diseases Inc., 7367 Wexford Terrace, Boca Raton, FL, USA. boneal@winning.com.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Weinreb
authors.affiliation: Childrens Hospital of Pittsburgh, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. dnf@pitt.edu.
authors.forename: David N
authors.initials: DN
authors.lastname: Finegold
authors.affiliation: University of Pittsburgh, 623 Parran Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. Feingold@pitt.edu.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
authors.affiliation: University of Pittsburgh, 623 Parran Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. zhenhouse@msn.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Tower Cancer Research Foundation, 9090 Wilshire Blvd., Suite 350, Beverly Hills, CA, 90211, USA. rosenbloomb@toweroncology.com.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Rosenbloom
authors.affiliation: Emory University School of Medicine, 2165 North Decatur Rd, Atlanta, GA, 30033, USA. suma.shankar@emory.edu.
authors.forename: Suma P
authors.initials: SP
authors.lastname: Shankar
authors.affiliation: Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. damato@mtsinai.on.ca.
authors.forename: Dominick
authors.initials: D
authors.lastname: Amato
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000235:genetics / Q000473:pathology*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult