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

Orphanet Journal of Rare Diseases

Nadia Belmatoug^1,10  France Mentré⁸  Thierry Billette de Villemeur^1,16  Bruno Fantin^1,10  Olivier Fain^1,14  Vassili Valayanopoulos²  Marie T Vanier^1,15  Dries Dobbelaere^1,18  Frédéric Sedel^1,16  Cyril Mignot^1,16  Agathe Masseau⁴  Thierry Levade^1,17  Roselyne Froissart¹  Catherine Caillaud^1,16  Alain Robert⁶  Pierre Kaminsky^1,12  Bernard Grosbois³  Christine de Roux-Serratrice^1,11  Fabrice Camou⁷  Christian Rose^1,19  Marc G Berger⁵  Linda Rossi-Semerano⁹  Djazia Heraoui^1,10  Dalil Hamroun^1,13  Marie Vigan⁸  Jérôme Stirnemann^1,14 

[1] Centre de Biologie Est, Hospices Civils de Lyon, Bron, France;Centre de Référence Maladies Métaboliques de l'Enfant et de Adulte (MaMEA), Hôpital Necker-Enfants Malades et Université Paris, Descartes, Paris, France;Service de Médecine Interne, Etablissements Nord Sud, Site Hôpital Sud, Rennes, France;Service de Médecine Interne, CHU Hôtel-Dieu, Nantes, France;Service d'Hématologie Biologique–Immunologie, CHU Estaing, Clermont-Ferrand, France;Service de Pédiatrie, Hôpital des Enfants, Toulouse, France;Service de Réanimation Médicale, CHU Saint-André, Bordeaux, France;Univ Paris-Diderot, Sorbonne Paris Cité, Paris, France, INSERM, UMR, Paris, 738, France;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;Service de Médecine Interne, Hôpital Beaujon, AP–HP, Clichy, France;Service de Médecine Interne, Hôpital Saint-Joseph, Marseille, France;Service de Médecine Interne, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre, France;Laboratoire de Génétique Moléculaire CHU Montpellier, Hôpital Arnaud-de-Villeneuve, Montpellier, France;Hôpitaux Universitaires Paris Seine–Saint-Denis, AP–HP Service de Médecine Interne, Hôpital Jean-Verdier, Université, Paris XIII, Bondy, France;INSERM U 820, Faculté de Médecine Lyon-Est Claude-Bernard, Lyon, France;Referral Center for Lysosomal Diseases (RCLD), Paris, France;Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France;Centre de Référence des Maladies Héréditaires du Métabolisme de l’Enfant et de l’Adulte, Hôpital Jeanne-de-Flandre, Lille, France;Service d’Hématologie, Hôpital Saint-Vincent-de-Paul, Lille, France

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

Others  :  864193
DOI  :  10.1186/1750-1172-7-77

 received in 2012-01-15, accepted in 2012-10-07,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Stirnemann et al.; licensee BioMed Central Ltd.

【 图 表 】

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