How is the severity of Gaucher disease assessed?

Published in 1989, the Zimran Severity Score Index (SSI) was developed to assess the severity of Gaucher disease according to age at diagnosis and extent of organ involvement.1 This index was subsequently modified and published in 1992 where the clinical, laboratory, radiological and genetic features of 53 patients with Gaucher disease were followed.2 However, the Zimran SSI has not been tested with contemporary methods to assess performance parameters, nor has its responsiveness to intra-patient changes in disease manifestations over time been established. Consequently, the Zimran SSI has not been widely used in routine clinical practice or as an endpoint in clinical trials.3

The Gaucher Disease Severity Score Index – Type I (GauSSI-I) was developed and published in 2008. This scoring system was based on the clinical experience of the authors and an extensive review of the literature, including data from the International Gaucher Registry. Although the GauSSI-I was shown to be a reliable method for staging the severity of Gaucher disease Type 1 in adults, and more sensitive than the Zimran SSI for monitoring response to treatment, it was not validated.4 It was suggested that the use of the GauSSI-I may be limited due to its complexity and the technological requirements of some of the components of the assessments, and therefore it may be more useful in situations of limited applications, such as single-centre clinical trials.3

A validated disease severity scoring system (DS3) for adults with Gaucher disease Type 1 (GD1-DS3) was published in 2010.3

GD1-DS3 for adults with Gaucher disease Type 1

For the development of the GD1-DS3, DS3 domains were determined by an expert group of physicians using the nominal group technique of consensus formation. Items of the DS3 were selected by 36 physicians with experience in Gaucher disease Type 1. The expert group determined appropriate measurement techniques for each item; measurements were weighted to consider contributions to morbidity and mortality associated with Gaucher disease Type 1. Consensus Global Impression Severity scores for sample cases were compared with average DS3 scores; a minimal clinically important difference in Gaucher disease Type 1 DS3 scores was then calculated.3

The GD1-DS3 contains three domains: bone, haematological and visceral. Each domain contains ≥3 items, each scored individually by the evaluating physician. The domain score is then tabulated by averaging the scores for all items within the domain. A total GD1-DS3 score is the sum of the three domain scores, with a maximum score of 19 points.3

 

Using routine assessments including medical history, blood chemistry, organ-volume measurements and bone evaluations (via magnetic resonance imaging and dual X-ray absorptiometry), results of the GD1-DS3 may be interpreted as follows3:

  • 0‒3: borderline to mild disease
  • 3‒6: moderate disease
  • 6‒9: marked disease
  • 9+: severe disease

Initial estimates of validity, reliability and theoretical feasibility suggested that the GD1-DS3 is a practicable and reliable instrument for assessing the disease severity and progression of Gaucher disease Type 1.3


A severity scoring tool (SST) assesses the neurological features of Gaucher disease Type 3

In 2007, an SST was developed and published to monitor neurological manifestations of Gaucher disease Type 3. This tool was developed using neurological domain identification, item generation and tool formation. Domain identification was based on a retrospective single-centre study of 15 patients with Gaucher disease Type 3 and a systematic review of the literature. In total, 47 patients with Gaucher disease Type 3 were assessed using the tool to determine the clinical and statistical reliability of each domain. Content validity was assessed via judgement quantification by five European experts.5

Categories of severity were defined for each of the original identified features and weighted with equal scores from 0 to 3, with 3 indicating the more severe presentation of that feature. A total score of 39 indicated the most severe form of the disease overall.5 

Overall, the final SST was proposed by the authors to be concise and user-friendly in the evaluation of the neurological manifestations of patients with Gaucher disease Type 3, and demonstrated validity in clinical practice.5

C-ANPROM/INT//7567; Date of preparation: September 2020