Schaison Gérard, Caubel Isabelle, Belmatoug Nadia, Billette de Villemeur Thierry, Saudubray Jean-Marie
Service de Pédiatrie à Orientation hématologique-Hôpital Saint Louis-1, avenue Claude Vellefaux-75475 Paris.
Bull Acad Natl Med. 2002;186(5):851-61; discussion 861-3.
Gaucher disease is an inborn recessive autosomal disease due to a partial deficiency of the lysosomal enzyme beta glucocerebrosidase. The deficient activity leads to accumulation of the lipid glucocerebroside in the liver, the spleen and bone marrow with concomitant anemia and thrombocytopenia. Patients with Gaucher disease have been classified in three types: type I is the more common, neurological manifestations occur in types II and III. Enzyme replacement therapy (ERT) with modified placental human glucocerebrosidase (ceredase) or recombinant glucocerebrosidase (cerezyme) is effective in most type I Gaucher disease and has become the current standard care administered to thousand of patients worldwide. ERT has obviated the need for bone marrow transplantation and virtually eliminated the need for splenectomy. We report here the French study including adults and children. ERT of 30 to 60 U/K every two weeks as starting dose was administrated to 108 patients with severe type I Gaucher disease. ERT fully reverse many of the manifestations of the disease. ERT regimen alleviated fatigue, and hematological and visceral signs and symptoms in nearly all severely-ill patients. Skeletal responses to treatment develop much more slowly than hematological or visceral responses. Studies in pediatrics show that the disease is more severe in children. These children should be treated early in the course of their disease to avoid irreparable damage. Hematological manifestation in type II cannot be reversed with enzyme replacement. In type III treatment can rarely reverse neurological deficit. Gaucher disease is also an excellent candidate for gene therapy.
戈谢病是一种常染色体隐性遗传病，由于溶酶体酶β-葡萄糖脑苷脂酶部分缺乏所致。酶活性缺乏导致脂质葡萄糖脑苷脂在肝脏、脾脏和骨髓中蓄积，同时伴有贫血和血小板减少。戈谢病患者分为三型：I型最为常见，II型和III型有神经系统表现。用改良的胎盘人葡萄糖脑苷脂酶（思而赞）或重组葡萄糖脑苷脂酶（美而赞）进行酶替代疗法（ERT）对大多数I型戈谢病有效，已成为全球数千名患者目前的标准治疗方法。ERT已不再需要进行骨髓移植，几乎消除了脾切除术的必要性。我们在此报告一项纳入成人和儿童的法国研究。起始剂量为每两周30至60 U/K的ERT应用于108例重度I型戈谢病患者。ERT完全逆转了该疾病的许多表现。ERT方案缓解了几乎所有重症患者的疲劳以及血液学和内脏体征及症状。骨骼对治疗的反应比血液学或内脏反应发展得慢得多。儿科研究表明，该疾病在儿童中更为严重。这些儿童应在疾病早期接受治疗，以避免不可挽回的损害。II型的血液学表现不能通过酶替代逆转。在III型中，治疗很少能逆转神经功能缺损。戈谢病也是基因治疗的极佳候选对象。
