A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease

1 Rare Disease Unit, II Division of Pediatrics, Gaslini Institute, Genoa, Italy 2 Department of Cellular Biotechnologies and Hematology, "La Sapienza" University, Rome, Italy 3 Department of Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, Modena, Italy 4 Agency for Hemophilia and Regional Reference Center for Inherited Bleeding Disorders, "Careggi" University Hospital, Florence, Italy 5 Section of Epidemiology and Statistics, CNR Institute of Clinical Physiology, Pisa, Italy 6 Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA 7 Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy 8 Department of Internal Medicine "Policlinico Mangiagalli Regina Elena" Foundation IRCCS, University of Milan, Milan, Italy Correspondence: Maja Di Rocco, MD Rare Disease Unit, II Division of Pediatrics, Gaslini Institute Largo Gerolamo Gaslini 5, 16147, Genova, Italy. E-mail: majadirocco{at}ospedale-gaslini.ge.it Background: Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment. Design and Methods: The new scoring system proposed here, the "Gaucher Disease Severity Score Index – Type I" (GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods on an equivalent basis. Results: The new scoring system, GauSSI-I, was developed. Six specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available. Conclusions: The GauSSI-I is a reliable metho