CRIM Responses in Pompe Disease

Pompe病(糖原蓄积症II型；MIM 232300)是一种典型的溶酶体蓄积性疾病 这会导致婴儿形式的患者在生命的第一年死于进行性的 心肌病导致心肺衰竭。肌酶(α-葡萄糖苷酶，重组人 酸性α-葡萄糖苷酶/GAA，rhGAA)于2006年4月被批准用于治疗庞贝病。这个 使用Myozyme的ERT改善了大多数庞培病患者的预后；然而， 一组婴儿庞培患者对ERT的反应很差，随后死于心肺疾病 失败了。反应不佳的庞贝病患者通常缺乏残存的GAA表达，这些 患者交叉反应免疫物质阴性(CRIM阴性)。 这项提案的目的是评估这些罕见的CRIM阴性庞贝病患者的ERT+/- 免疫抑制，通过将他们纳入前瞻性/回溯性自然历史研究 溶酶体疾病网络。受试者将从网络中登记，并收集关于 临床终点的数量来确定这种疾病的自然病史。登记将包括患者 对于他们来说，对当前治疗的临床反应预计会很差。被研究的患者都是婴儿交叉反应 免疫材料(CRIM)阴性的庞贝病患者服用临床方案启动酶 有或没有免疫抑制的替代疗法(ERT)。这些数据将与所获得的数据进行比较 从婴儿Crim阳性的庞贝病患者开始接受ERT的年龄相似，也参加了 ERT上监测疾病病史和转归的方案。

Pompe disease (Glycogen storage disease type II; MIM 232300) is a classical lysosomal storage disorder that causes death in the first year of life for patients with the infantile form due to a progressive cardiomyopathy leading to cardiorespiratory failure. Myozyme (alglucosidase alpha, recombinant human acid alpha-glucosidase/GAA, rhGAA) was approved in April 2006 as a treatment for Pompe Disease. The availability of ERT with Myozyme has improved the outcome of most patients with Pompe disease; however, a subset of infantile Pompe patients responds poorly to ERT, subsequently dying from cardiorespiratory failure. Poorly-responding Pompe disease patients generally lack residual GAA expression and these patients are cross-reacting immune material-negative (CRIM-negative). The Aims of this proposal would evaluate these rare CRIM-negative Pompe disease patients on ERT +/- immune suppression, by enrolling them in a prospective/retrospective natural history study through the Lysosomal Disease Network. Subjects would be enrolled from the Network and data collected regarding a number of clinical endpoints to determine the natural history of this disorder. Enrollment will include patients for whom a poor clinical response to current therapy is predicted. Patients studied will be all infantile crossreacting immune material (CRIM)-negative Pompe disease patients on a clinical protocol starting enzyme replacement therapy (ERT) with or without immune suppression. They will be compared to data obtained from infantile CRIM-positive Pompe disease patients started on ERT at similar ages and also enrolled in the protocol monitoring history and outcome of the disease on ERT.