Open Access Highly Accessed Research

The French Gaucher’s disease registry: clinical characteristics, complications and treatment of 562 patients

Jérôme Stirnemann122534*, Marie Vigan12, Dalil Hamroun5, Djazia Heraoui36, Linda Rossi-Semerano7, Marc G Berger8, Christian Rose9, Fabrice Camou10, Christine de Roux-Serratrice11, Bernard Grosbois12, Pierre Kaminsky13, Alain Robert14, Catherine Caillaud153, Roselyne Froissart16, Thierry Levade17, Agathe Masseau18, Cyril Mignot19203, Frédéric Sedel213, Dries Dobbelaere22, Marie T Vanier23, Vassili Valayanopoulos24, Olivier Fain4, Bruno Fantin26, Thierry Billette de Villemeur203, France Mentré12 and Nadia Belmatoug36

Author Affiliations

1 INSERM, UMR 738, Laboratoire de Biostatistiques Hôpital Bichat, Assistance PubliqueHôpitaux de Paris (AP–HP), Paris, France

2 Univ Paris-Diderot, Sorbonne Paris Cité, Paris, France, INSERM, UMR, Paris, 738, France

3 Referral Center for Lysosomal Diseases (RCLD), Paris, France

4 Hôpitaux Universitaires Paris Seine–Saint-Denis, AP–HP Service de Médecine Interne, Hôpital Jean-Verdier, Université, Paris XIII, Bondy, France

5 Laboratoire de Génétique Moléculaire CHU Montpellier, Hôpital Arnaud-de-Villeneuve, Montpellier, France

6 Service de Médecine Interne, Hôpital Beaujon, AP–HP, Clichy, France

7 Service de Pédiatrie et Pédiatrie Rhumatologique, Hôpital de Bicêtre, AP–HP, National Reference Center for Auto-Inflammatory Diseases, Université de Paris Sud, Le Kremlin–Bicêtre, France

8 Service d'Hématologie Biologique–Immunologie, CHU Estaing, Clermont-Ferrand, France

9 Service d’Hématologie, Hôpital Saint-Vincent-de-Paul, Lille, France

10 Service de Réanimation Médicale, CHU Saint-André, Bordeaux, France

11 Service de Médecine Interne, Hôpital Saint-Joseph, Marseille, France

12 Service de Médecine Interne, Etablissements Nord Sud, Site Hôpital Sud, Rennes, France

13 Service de Médecine Interne, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre, France

14 Service de Pédiatrie, Hôpital des Enfants, Toulouse, France

15 Laboratoire de Génétique, Hôpital Cochin, Paris, France

16 Centre de Biologie Est, Hospices Civils de Lyon, Bron, France

17 Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France

18 Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France

19 Unité Fonctionnelle de Génétique Clinique, Groupe Hospitalier Pitié–Salpêtrière, AP–HP, Paris, France

20 Service de Neuropédiatrie et Pathologie du Développement, Hôpital Armand-Trousseau, AP–HP, Université Pierre-et-Marie-Curie UPMC, Paris, France

21 Département de Neurologie, Hôpital Pitié–Salpêtrière, AP–HP, Paris, France

22 Centre de Référence des Maladies Héréditaires du Métabolisme de l’Enfant et de l’Adulte, Hôpital Jeanne-de-Flandre, Lille, France

23 INSERM U 820, Faculté de Médecine Lyon-Est Claude-Bernard, Lyon, France

24 Centre de Référence Maladies Métaboliques de l'Enfant et de Adulte (MaMEA), Hôpital Necker-Enfants Malades et Université Paris, Descartes, Paris, France

25 Hôpitaux Universitaires de Genève, Service de Médecine Interne Générale, Rue Gabrielle-Perret-Gentil 4, CH-1211, Genève 14, Suisse

For all author emails, please log on.

Orphanet Journal of Rare Diseases 2012, 7:77  doi:10.1186/1750-1172-7-77

Published: 9 October 2012

Abstract

Background

Clinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.

Methods

All patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.

Results

Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%).

Conclusion

This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.

Keywords:
French Gaucher’s Disease Registry; Bone events; Enzyme-replacement therapy