D. Remiremont-) and . Hama, Fabre Sylvie (Montpellier), Feillet François (Vandoeuvre-les-Nancy), Ferry Régine (Charleville-Mézières), Flodrops Hugues (Saint-Pierre, Dobbelaere Dries (Lilles) Edan Christine (Rennes) Gaches Francis (Toulouse), Gay Claire (Saint-Étienne), Germain Dominique (Garches), Gil Helder Guérin Jacques (Arpajon), Guillaumat Cécile (Corbeil?Éssonne)

H. Raoul, Kpati Agbo (Lagny-sur-Marne) Kuster Alice (Nantes), Lackmy-Port-Lis Marylin (Pointe-à-Pitre), Jourdan Éric (Nîmes) Lavigne Christian (Angers)

L. Michel-(-caen-), L. Brigitteparis-), and L. Marc, Oksenhendler Éric (Paris) Orzechowski Christine (Bry-sur-Marne) Oudot Caroline (Paris), Pan, Lidove Olivier Morel Pierre (Lens), Navarro Robert (Montpellier), Ninet Jacques (Lyon), Noël Esther Plouvier Emmanuel Savoye Guillaume Sedel Frédéric Solary Éric (Dijon) Tchamgoue Serge (Libourne) Tieule Nathalie (Nice)

V. Laurent, Zunic Patricia (Saint-Pierre) The salaries of a statistician and a clinical research associate who participated in this study were funded, in part, by a grant from Genzyme France Genzyme played no role in designing the study; in collecting, analyzing and interpreting the data; writing the paper; or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval of the study's sponsors. The development of the original software for the French Gaucher Disease Registry (FGDR) was funded by a grant from the association VML (Vaincre les Maladies Lysosomales). J. Stirnemann's work was funded, Zenone Thierry (Valence), p.from INSERM

S. Paris and C. , 4 Hôpitaux Universitaires Paris Seine?Saint-Denis, Referral Center for Lysosomal Diseases (RCLD), issue.6 7

. Service-de-pédiatrie-et-pédiatrie-rhumatologique, Le Kremlin?Bicêtre, France. 8 Service d'Hématologie Biologique?Immunologie, CHU Estaing, Clermont-Ferrand, France. 9 Service d'Hématologie, Hôpital Saint-Vincent-de-Paul, p.13

A. Hp, U. Pierre-et-marie-curie, and U. , 22 Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Hôpital Jeanne-de-Flandre, 21 Département de Neurologie, Hôpital Pitié?Salpêtrière 24 Centre de Référence Maladies Métaboliques de l'Enfant et de Adulte (MaMEA), p.1211

R. 1. Brady, R. Kanfer, J. Shapiro, and D. , Metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher's disease, Biochemical and Biophysical Research Communications, vol.18, issue.2, pp.221-225, 1965.
DOI : 10.1016/0006-291X(65)90743-6

O. Staretz-chacham, T. Lang, M. Lamarca, D. Krasnewich, and E. Sidransky, Lysosomal Storage Disorders in the Newborn, PEDIATRICS, vol.123, issue.4, pp.1191-1207, 2009.
DOI : 10.1542/peds.2008-0635

H. Christomanou, A. Aignesberger, and R. Linke, Immunochemical Characterization of Two Activator Proteins Stimulating Enzymic Sphingomyelin Degradation in vitro Absence of One of them in a Human Gaucher Disease Variant, Biological Chemistry Hoppe-Seyler, vol.367, issue.2, pp.879-890, 1986.
DOI : 10.1515/bchm3.1986.367.2.879

X. Qi and G. Grabowski, Molecular and cell biology of acid ??-glucosidase and prosaposin, Prog Nucleic Acid Res Mol Biol, vol.66, pp.203-239, 2001.
DOI : 10.1016/S0079-6603(00)66030-0

G. Grabowski, Recent clinical progress in Gaucher disease, Current Opinion in Pediatrics, vol.17, issue.4, pp.519-524, 2005.
DOI : 10.1097/01.mop.0000172702.33128.19

I. Kraoua, J. Stirnemann, M. Ribeiro, T. Rouaud, M. Verin et al., Parkinsonism in Gaucher's disease type 1: Ten new cases and a review of the literature, Movement Disorders, vol.70, issue.10, pp.1524-1530, 2009.
DOI : 10.1002/mds.22593

C. Mignot, D. Doummar, M. I. De-villemeur, and T. , Type 2 Gaucher disease: 15 new cases and review of the literature, Brain and Development, vol.28, issue.1, pp.39-48, 2006.
DOI : 10.1016/j.braindev.2005.04.005

M. Eblan, O. Goker-alpan, and E. Sidransky, PERINATAL LETHAL GAUCHER DISEASE: A DISTINCT PHENOTYPE ALONG THE NEURONOPATHIC CONTINUUM, Fetal and Pediatric Pathology, vol.93, issue.4-5, pp.205-222, 2005.
DOI : 10.1056/NEJM199706263362608

C. Mignot, A. Gelot, B. Bessieres, F. Daffos, M. Voyer et al., Perinatal-lethal Gaucher disease, American Journal of Medical Genetics Part A, vol.43, issue.3, pp.338-344, 2003.
DOI : 10.1002/ajmg.a.20117

C. Hollak, S. Van-weely, M. Van-oers, and J. Aerts, Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease., Journal of Clinical Investigation, vol.93, issue.3, pp.1288-1292, 1994.
DOI : 10.1172/JCI117084

P. Deegan, M. Moran, I. Mcfarlane, J. Schofield, R. Boot et al., Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease, Blood Cells, Molecules, and Diseases, vol.35, issue.2, pp.259-267, 2005.
DOI : 10.1016/j.bcmd.2005.05.005

J. Lieberman and E. Beutler, Elevation of Serum Angiotensin-Converting Enzyme in Gaucher's Disease, New England Journal of Medicine, vol.294, issue.26, pp.1442-1444, 1976.
DOI : 10.1056/NEJM197606242942609

A. Zimran, A. Kay, T. Gelbart, P. Garver, D. Thurston et al., Gaucher Disease, Medicine, vol.71, issue.6, pp.337-353, 1992.
DOI : 10.1097/00005792-199211000-00002

M. Morgan, A. Hoffbrand, M. Laulicht, W. Luck, and S. Knowles, Serum ferritin concentration in Gaucher's disease., BMJ, vol.286, issue.6381, p.1864, 1983.
DOI : 10.1136/bmj.286.6381.1864

L. Tuchman, H. Suna, and J. Carr, Elevation of serum acid phosphatase in Gaucher's disease, Journal of Mount Sinai Hospital, vol.23, pp.227-229, 1956.

K. Troy, J. Cuttner, M. Reilly, G. Grabowski, and R. Desnick, Tartrate-resistant acid phosphatase staining of monocytes in gaucher disease, American Journal of Hematology, vol.80, issue.3, pp.237-244, 1985.
DOI : 10.1002/ajh.2830190305

N. Barton, R. Brady, J. Dambrosia, D. Bisceglie, A. Doppelt et al., Replacement Therapy for Inherited Enzyme Deficiency ??? Macrophage-Targeted Glucocerebrosidase for Gaucher's Disease, New England Journal of Medicine, vol.324, issue.21, pp.1464-1470, 1991.
DOI : 10.1056/NEJM199105233242104

A. Zimran, G. Altarescu, M. Philips, D. Attias, M. Jmoudiak et al., Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience, Blood, vol.115, issue.23, pp.4651-4656, 2010.
DOI : 10.1182/blood-2010-02-268649

Y. Shaaltiel, D. Bartfeld, S. Hashmueli, G. Baum, E. Brill-almon et al., Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system, Plant Biotechnology Journal, vol.138, issue.5, pp.579-590, 2007.
DOI : 10.1016/0168-9452(89)90232-X

J. Aerts, C. Hollak, R. Boot, J. Groener, and M. Maas, Substrate reduction therapy of glycosphingolipid storage disorders, Journal of Inherited Metabolic Disease, vol.11, issue.2-3, pp.449-456, 2006.
DOI : 10.1007/s10545-006-0272-5

C. Hollak, V. Dahl, S. Aerts, J. Belmatoug, N. Bembi et al., Force Majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease, Blood Cells, Molecules, and Diseases, vol.44, issue.1, pp.41-47, 2010.
DOI : 10.1016/j.bcmd.2009.09.006

J. Charrow, H. Andersson, P. Kaplan, E. Kolodny, P. Mistry et al., The Gaucher Registry, Archives of Internal Medicine, vol.160, issue.18, pp.2835-2843, 2000.
DOI : 10.1001/archinte.160.18.2835

P. Giraldo, M. Pocovi, J. Perez-calvo, D. Rubio-felix, and M. Giralt, Report of the Spanish Gaucher's disease registry: clinical and genetic characteristics, Haematologica, vol.85, pp.792-799, 2000.

P. Giraldo, P. Alfonso, P. Irun, L. Gort, A. Chabas et al., Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula, Orphanet Journal of Rare Diseases, vol.7, issue.1, p.17, 2012.
DOI : 10.1590/S0100-879X2006000900004

E. Sobreira, R. Pires, M. Cizmarik, and G. Grabowski, Phenotypic and genotypic heterogeneity in Gaucher disease type 1: A comparison between Brazil and the rest-of-the-world, Molecular Genetics and Metabolism, vol.90, issue.1, pp.81-86, 2007.
DOI : 10.1016/j.ymgme.2006.08.009

Y. Eto and H. Ida, Clinical and molecular characteristics of Japanese Gaucher disease, Neurochemical Research, vol.24, issue.2, pp.207-211, 1999.
DOI : 10.1023/A:1022553819241

P. Mistry, N. Weinreb, P. Kaplan, J. Cole, A. Gwosdow et al., Osteopenia in Gaucher disease develops early in life: Response to imiglucerase enzyme therapy in children, adolescents and adults, Blood Cells, Molecules, and Diseases, vol.46, issue.1, pp.66-72, 2011.
DOI : 10.1016/j.bcmd.2010.10.011

B. Rosenbloom, M. Balwani, J. Bronstein, E. Kolodny, S. Sathe et al., The incidence of Parkinsonism in patients with type 1 Gaucher disease: Data from the ICGG Gaucher Registry, Blood Cells, Molecules, and Diseases, vol.46, issue.1, pp.95-102, 2011.
DOI : 10.1016/j.bcmd.2010.10.006

A. Tylki-szymanska, A. Vellodi, A. El-beshlawy, J. Cole, and E. Kolodny, Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry, Journal of Inherited Metabolic Disease, vol.8, issue.4, pp.339-346, 2010.
DOI : 10.1007/s10545-009-9009-6

N. Weinreb, P. Deegan, K. Kacena, P. Mistry, G. Pastores et al., Life expectancy in Gaucher disease type 1, American Journal of Hematology, vol.90, issue.12, pp.896-900, 2008.
DOI : 10.1002/ajh.21305

C. Fairley, A. Zimran, M. Phillips, M. Cizmarik, Y. J. Weinreb et al., Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: An analysis of 798 patients from the ICGG Gaucher Registry, Journal of Inherited Metabolic Disease, vol.66, issue.6, pp.738-744, 2008.
DOI : 10.1007/s10545-008-0868-z

N. Weinreb, J. Taylor, T. Cox, and Y. J. , A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase, American Journal of Hematology, vol.16, issue.12, pp.890-895, 2008.
DOI : 10.1002/ajh.21280

R. Wenstrup, K. Kacena, P. Kaplan, G. Pastores, A. Prakash-cheng et al., Effect of Enzyme Replacement Therapy With Imiglucerase on BMD in Type 1 Gaucher Disease, Journal of Bone and Mineral Research, vol.353, issue.Suppl 1, pp.119-126, 2007.
DOI : 10.1359/jbmr.061004

L. Daniels and R. Glew, Beta-glucosidase assays in the diagnosis of Gaucher's disease, Clin Chem, vol.28, pp.569-577, 1982.

J. Stirnemann, N. Belmatoug, C. Vincent, O. Fain, B. Fantin et al., Bone events and evolution of biologic markers in Gaucher disease before and during treatment, Arthritis Research & Therapy, vol.12, issue.4, p.156, 2010.
DOI : 10.1186/ar3111
URL : https://hal.archives-ouvertes.fr/inserm-00544232

P. Mistry, P. Deegan, A. Vellodi, J. Cole, M. Yeh et al., Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis, British Journal of Haematology, vol.9, issue.Suppl. 1, pp.561-570, 2009.
DOI : 10.1111/j.1365-2141.2009.07872.x

T. Cox and J. Schofield, 3 Gaucher's disease: clinical features and natural history, Bailli??re's Clinical Haematology, vol.10, issue.4, pp.657-689, 1997.
DOI : 10.1016/S0950-3536(97)80033-9

L. Lacerda, O. Amaral, R. Pinto, J. Aerts, S. Miranda et al., The N370S mutation in the glucocerebrosidase gene of Portuguese type 1 Gaucher patients: Linkage to the PvuII polymorphism, Journal of Inherited Metabolic Disease, vol.46, issue.1, pp.85-88, 1994.
DOI : 10.1007/BF00735401

G. Bultron, K. Kacena, D. Pearson, M. Boxer, R. Yang et al., The risk of Parkinson???s disease in type??1 Gaucher disease, Journal of Inherited Metabolic Disease, vol.34, issue.2, pp.167-173, 2010.
DOI : 10.1007/s10545-010-9055-0

A. Brautbar, D. Elstein, G. Pines, A. Abrahamov, and A. Zimran, Effect of enzyme replacement therapy on gammopathies in Gaucher disease, Blood Cells, Molecules, and Diseases, vol.32, issue.1, pp.214-217, 2004.
DOI : 10.1016/j.bcmd.2003.10.007

B. Grosbois, C. Rose, E. Noel, C. De-roux-serratrice, D. Dobbelaere et al., Gaucher disease and monoclonal gammopathy: A report of 17 cases and impact of therapy, Blood Cells, Molecules, and Diseases, vol.43, issue.1, pp.138-139, 2009.
DOI : 10.1016/j.bcmd.2009.04.002

D. Fost, M. Out, T. De-wilde, F. Tjin, E. Pals et al., Immunoglobulin and free light chain abnormalities in Gaucher disease type I: data from an adult cohort of 63 patients and review of the literature, Annals of Hematology, vol.31, issue.6, pp.439-449, 2008.
DOI : 10.1007/s00277-008-0441-8

K. Sims, G. Pastores, N. Weinreb, J. Barranger, B. Rosenbloom et al., Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study, Clinical Genetics, vol.146, issue.12, pp.430-440, 2008.
DOI : 10.1111/j.1399-0004.2008.00978.x