title: A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.
abstract: Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in theGBA1gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD-but also carriers ofGBA1mutation-have been found to be predisposed to developing Parkinson's disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat).
authors.affiliation: Department of Internal Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH-1211 Genève, Switzerland. jerome.stirnemann@hcuge.ch.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Stirnemann
authors.affiliation: Department of Internal Medicine, Reference Center for Lysosomal Storage Diseases, Hôpitaux Universitaires Paris Nord Val de Seine, site Beaujon, Assistance Publique-Hôpitaux de Paris, 100 boulevard du Général Leclerc, F-92110 Clichy la Garenne, France. nadia.belmatoug@aphp.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.affiliation: Réanimation Médicale, Hôpital Saint André, CHU de Bordeaux, 1 rue Jean Burguet, F-33075 Bordeaux, France. fabrice.camou@chu-bordeaux.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Camou
authors.affiliation: Department of Internal Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH-1211 Genève, Switzerland. christine.serratrice@hcuge.ch.
authors.forename: Christine
authors.initials: C
authors.lastname: Serratrice
authors.affiliation: Service de Biochimie et Biologie Moléculaire Grand Est, unité des Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, F-69677 Bron, France. roseline.froissart@chu-lyon.fr.
authors.forename: Roseline
authors.initials: R
authors.lastname: Froissart
authors.affiliation: Inserm U1151, Institut Necker Enfants Malades, Université Paris Descartes, Laboratoire de Biochimie, Métabolomique et Protéomique, Hôpital Universitaire Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, 149 rue de Sèvres, F-75005 Paris, France. catherine.caillaud@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillaud
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Paul Sabatier, Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, F-31059 Toulouse, France. levade.t@chu-toulouse.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Equipe Labellisée Ligue Contre le Cancer 2013, Centre de Recherches en Cancerologie de Toulouse (CRCT), Université de Toulouse, Service de Médecine Interne, CHU Purpan, F-31059 Toulouse, France. leonardo.astudillo31@gmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Astudillo
authors.affiliation: Department of Internal Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH-1211 Genève, Switzerland. jacques.serratrice@hcuge.ch.
authors.forename: Jacques
authors.initials: J
authors.lastname: Serratrice
authors.affiliation: Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte (MaMEA), Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Institut Imagine, F-75012 Paris, France. anais.brassier@nck.aphp.fr.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Brassier
authors.affiliation: Service d'onco-hématologie, Saint-Vincent de Paul Hospital, Boulevard de Belfort, Université Catholique de Lille, Univ. Nord de France, F-59000 Lille, France. Rose.Christian@ghicl.net.
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
authors.affiliation: Service de Neuropédiatrie, Pathologie du développement, Sorbonne Université, Reference Center for Lysosomal Diseases, Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris, 24 Avenue du docteur Arnold Netter, F-75012 Paris, France. thierry.billette@aphp.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Billette de Villemeur
authors.affiliation: CHU Estaing et Université Clermont Auvergne, Hematology (Biology) et EA 7453 CHELTER, F-63000 Clermont-Ferrand, France. mberger@chu-clermontferrand.fr.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Berger
mesh_terms: D005776:Gaucher Disease / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008991:Monitoring, Physiologic; D011379:Prognosis
keywords: GBA1 gene; Gaucher disease; biomarkers; enzyme replacement therapy; glucocerebrosidase; lysosomal storage disease; substrate reduction therapy