戈谢病

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戈谢病

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PubMed ID

20301446 (在PubMed

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文摘

戈谢病(GD)包含一个连续体的临床发现无症状的围产期致命障碍类型。三个主要临床类型的识别(1、2和3)和另外两个亚型(perinatal-lethal和心血管)是有用的在决定预后和管理。GD 1型的特点是骨病的临床或影像学证据的存在(骨量减少、裂解或僵化的局灶性病变和骨坏死),肝脾肿大,贫血和血小板减少,肺部疾病,没有主要的中枢神经系统疾病。GD类型2和3的特点是存在的主要神经系统疾病;在过去,他们是杰出的发病的年龄和疾病进展,但这些区别不是绝对的。疾病发病年龄之前两年,有限的精神运动发展,快速进步是依靠两到四年课程与死亡年龄分为GD型2。GD患者类型3岁之前可能发生两年,但往往有一个更加缓慢渐进,与生存到第三或第四个十年。perinatal-lethal形式与ichthyosiform或胶皮肤异常或多发地胎儿水肿。心血管的形式特征是钙化的主动脉瓣和二尖瓣替换手术,轻度脾肿大,角膜混浊,核上的眼肌麻痹。描述了心肺并发症的临床亚型,尽管不同的频率和严重程度。 The diagnosis of GD relies on demonstration of deficient glucocerebrosidase (glucosylceramidase) enzyme activity in peripheral blood leukocytes or other nucleated cells. Carrier testing by assay of enzyme activity is unreliable because of overlap in enzyme activity between carriers and non-carriers. Identification of two disease-causing alleles in GBA, the only gene in which pathogenic variants are known to cause GD, provides additional confirmation of the diagnosis. However, given the broad heterogeneity in causative pathogenic variants, biochemical testing should be considered in individuals in whom genetic testing identifies a novel GBA pathogenic variant. Treatment of manifestations: When possible, management by a multidisciplinary team at a Comprehensive Gaucher Center. For persons not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT), symptomatic treatment includes partial or total splenectomy for massive splenomegaly and thrombocytopenia. Supportive care for all affected individuals may include: transfusion of blood products for severe anemia and bleeding, analgesics for bone pain, joint replacement surgery for relief from chronic pain and restoration of function, and oral bisphosphonates and calcium for osteoporosis. Prevention of primary manifestations: ERT is usually well tolerated and provides sufficient exogenous enzyme to overcome the block in the catabolic pathway, clearing the stored substrate, GL1, and thus reversing hematologic and liver/spleen involvement. Although bone marrow transplantation (BMT) had been undertaken in individuals with severe GD, primarily those with chronic neurologic involvement (GD type 3), this procedure has been largely superseded by ERT. Miglustat may be indicated in symptomatic individuals with GD type 1 who are not able to receive ERT. Prevention of secondary complications: The use of anticoagulants in individuals with severe thrombocytopenia and/or coagulopathy should be discussed with a hematologist to avoid the possibility of excessive bleeding. Surveillance: Recommendations for comprehensive serial monitoring have been published by the International Collaborative Gaucher Group Registry (ICGG) and other groups. Agents/circumstances to avoid: Nonsteroidal anti-inflammatory drugs (NSAIDs) in individuals with moderate to severe thrombocytopenia. Evaluation of relatives at risk: It is appropriate to offer testing to asymptomatic at-risk relatives so that those with glucocerebrosidase enzyme deficiency, or two disease-causing alleles, can benefit from early diagnosis and treatment if indicated. Gaucher disease (GD) is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Targeted mutation analysis can be used to detect carriers in high-risk populations (e.g., Ashkenazi Jewish persons). Because the carrier frequency for GD in certain populations is high (e.g., 1:18 in individuals of Ashkenazi Jewish heritage) and the N370S/N370S phenotype is variable, individuals who undergo carrier testing may be identified as being homozygous. Prenatal testing for pregnancies at increased risk is possible using assay of glucocerebrosidase enzymatic activity and molecular genetic testing when both disease-causing mutations in a family are known.

DrugBank数据引用了这篇文章

药物

Imiglucerase

药物靶点

药物	目标	类	生物	药理作用	行动
Alglucerase	物质	小分子	人类	是的	其他/未知	细节
Imiglucerase	物质	小分子	人类	是的	其他/未知	细节