Germain D P, Benistan K
Centre de référence de la maladie de Fabry et des maladies héréditaires du tissu conjonctif, Assistance Publique, Hôpitaux de Paris, Hôpital Raymond Poincaré, 104, Boulevard Raymond Poincaré, 92380 Garches, France.
Rev Med Interne. 2007 Oct;28 Suppl 2:S193-7. doi: 10.1016/s0248-8663(07)78881-1.
Gaucher disease (GD, OMIM #230800, 230900, 231000) is a lysosomal surcharge disorder caused by a deficiency in glucocerebrosidase, a lysosomal enzyme also referred to as acid beta-glucosidase or, in rare cases, by a deficiency in the activator protein saposin C. Partial deficiency of acid beta-glucosidase is associated with the presence of glucosylceramide, also known as glucocerebroside (Gb1), deposits in the reticuloendothelial cells of the liver, spleen and bone marrow, in non-neuronopathic type 1, GD. Profound deficiency of acid beta-glucosidase caused by disabling mutations is additionally associated with neurological manifestations in the less common type 2 and type 3 Gaucher diseases. Type 2 GD culminates in early death as a result of devastating neurological disease. Congenital ichtyosis with a collodion baby phenotype is also part of the spectrum of clinical presentations of type 2 GD. Recombinant glucocerebrosidase (imiglucerase) is an effective mean of treating type 1 GD and should be initiated early on in life. Although imiglucerase has recently been approved for the treatment of type 3 GD, enzyme replacement therapy cannot reverse the neurological manifestations in type 2 or type 3 GD. Following genetic counseling and informed consent, direct enzymatic assay of acid beta-glucosidase and molecular testing of the GBA mutations on chorionic villi samples (CVS) can be offered to families in which type 2 or type 3 GD has been diagnosed. Improvement in substrate deprivation therapy or gene therapy may provide a cure for patients with these disorders in the future.
戈谢病(GD,OMIM编号#230800、230900、231000)是一种溶酶体贮积症,由葡糖脑苷脂酶缺乏引起,该酶是一种溶酶体酶,也称为酸性β - 葡萄糖苷酶,在罕见情况下,由激活蛋白鞘磷脂C缺乏引起。酸性β - 葡萄糖苷酶部分缺乏与葡糖神经酰胺(也称为葡萄糖脑苷脂,Gb1)在肝、脾和骨髓的网状内皮细胞中沉积有关,这见于非神经病变性1型戈谢病。由失活突变导致的酸性β - 葡萄糖苷酶严重缺乏在较罕见的2型和3型戈谢病中还与神经学表现相关。2型戈谢病因严重的神经疾病最终导致早期死亡。具有胶样婴儿表型的先天性鱼鳞病也是2型戈谢病临床表现谱的一部分。重组葡糖脑苷脂酶(伊米苷酶)是治疗1型戈谢病的有效方法,应在生命早期开始使用。尽管伊米苷酶最近已被批准用于治疗3型戈谢病,但酶替代疗法不能逆转2型或3型戈谢病的神经学表现。在进行遗传咨询并获得知情同意后,对于已诊断出2型或3型戈谢病的家庭,可以提供对绒毛膜绒毛样本(CVS)进行酸性β - 葡萄糖苷酶的直接酶活性测定和GBA突变的分子检测。底物剥夺疗法或基因疗法的改进可能在未来为这些疾病的患者提供治愈方法。