A validated disease severity scoring system for adults with type 1 Gaucher disease.
OBJECTIVE
A validated disease severity scoring system (DS3) for Gaucher disease type 1 (GD1) is needed to standardize patient monitoring and to define patient cohorts in clinical studies.


METHODS
DS3 domains were established by an expert physician group using the nominal group technique of consensus formation. Items were selected by 36 GD1 physicians. The expert group determined appropriate measurement techniques for each item. Measurements were weighted considering contributions to GD1 morbidity and mortality. Consensus Clinical Global Impression Severity scores for sample cases were compared with average DS3 scores. A minimal clinically important difference in GD1 DS3 score was calculated.


RESULTS
The GD1 DS3 includes bone (42% of score), hematologic (32%), and visceral domains (26%); individual items use routine assessments, including medical history, blood chemistry, organ volume measurements, and bone evaluations (magnetic resonance imaging and dual x-ray absorptiometry). The maximum score is 19. Interrater reliability was 0.97 (Cohen's kappa). DS3 scores were highly correlated with Clinical Global Impression Severity scores (r2 = 0.89). The minimal clinically important difference was -3.2 improvement and +3.9 deterioration.


CONCLUSIONS
This DS3 accurately quantifies GD1 status and intrapatient change over time. Testing of reliability and validity will continue to allow eventual implementation of the DS3 in clinical studies and routine practice.
Weinreb
Neal J
NJ
University Research Foundation for Lysosomal Storage Disorders, Coral Springs, FL 33065, USA. boneal@winning.com
Cappellini
Maria D
MD
Cox
Timothy M
TM
Giannini
Edward H
EH
Grabowski
Gregory A
GA
Hwu
Wuh-Liang
WL
Mankin
Henry
H
Martins
Ana Maria
AM
Sawyer
Carolyn
C
vom Dahl
Stephan
S
Yeh
Michael S
MS
Zimran
Ari
A
D000328:Adult; D005776:Gaucher Disease / Q000145:classification / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D014644:Genetic Variation; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics; D015203:Reproducibility of Results; D012720:Severity of Illness Index
D005962:Glucosylceramidase