Basic research for the efficiency of enzyme therapy for glycogen storage disease type II (pompe disease)

糖原沉积病II型(Pompe病)是由于酸性α-葡萄糖苷酶缺乏导致糖原在多个组织中积聚而引起的。利用重组人酸性α-葡萄糖苷酶(RhGAA)进行酶治疗的报道显示，少数婴儿Pompe病的临床症状有所改善，而抗rhGAA抗体的产生可能会降低rhGAA治疗的有效性。一名两岁的日本Pompe病女孩参加了为期一年的rhGAA国际临床试验，并回到日本。我们成功地用日本Genzyme公司的rhGAA进行了酶疗法。她的心功能障碍正在改善，英国的一份报告显示没有产生抗rhGAA抗体。我们跟踪了她的临床病程并调查了遗传背景，以开发更有效的酶替代疗法。重组人GAA治疗庞贝病。我们在征得父母同意的情况下，每两周给一名患有庞贝病的日本三岁女孩注射一次。她经常患有呼吸道感染，有时由于感染或父母的不便，她的酶注射会被推迟。在推迟注射一个多月后，她患上了严重肺炎，需要机械通气支持和重症监护。在注射重组人生长激素和抗生素后，她康复了，但她需要进行气管切开和家庭氧疗。她现在严格每两周注射一次，心脏功能几乎正常。酸性α-葡萄糖苷酶基因突变分析：从患者皮肤成纤维细胞中提取DNA和总RNA，采用常规RT-PCR技术扩增人酸性α-葡萄糖苷酶基因。序列分析显示该基因存在796C&gt；T错义突变，已报道为病理性突变。对重组人免疫球蛋白A免疫原性的研究我们的患者在注射重组人免疫球蛋白A后，产生了抗重组人免疫球蛋白A抗体。我们对她免疫功能的分析是正常的。

Glycogen storage disease type II (Pompe disease) is caused by deficiency of acid alpha-glucosidase resulting in accumulations of glycogen in multiple tissues. Some reports of enzyme therapy using recombinant human acid alpha-glucosidase (rhGAA) showed clinical improvement of infantile Pompe disease in a few cases, and production of anti-rhGAA antibody might reduce the effectiveness of rhGAA therapy.A two years old Japanese girl with Pompe disease had attended a year of international clinical trial of rhGAA and came back to Japan. We succeeded her enzyme therapy with rhGAA (Genzyme Japan). Her cardiac dysfunction was improving and a report from UK suggests no anti-rhGAA antibody production. We followed her clinical course and investigate genetic background to develop more efficient enzyme for enzyme replacement therapy.1. rhGAA therapy for Pompe disease.We injected rhGAA every two weeks to a Japanese three years old girl with Pompe disease with agreement of her parents. She was often suffered from respiratory infections and her enzyme injection was sometimes postponed by reasons of her infections or her parents' inconvenience. After over a month of postpone of injection, she was affected with severe pneumonia and required mechanical ventilation support and intensive care. She had recovered with injection of rhGAA and antibiotics, however she required trachecstomy and home oxygen therapy. She now takes injection every two weeks strictly and her cardiac function is almost normal.2. Acid alpha-glucosidase gene mutation analysis.We extracted DNA and total RNA from patient's skin fibroblast and human acid alpha-glucosidase gene cDNA was amplified by conventional RT-PCR technique. Sequence analysis of cDNA showed a missence mutation (796C>T), which was already reported as pathological mutation.3. Investigation about immunogensity of rhGAA.After following injection of rhGAA, our patient produced anti-rhGAA antibody. Our analysis of her immune function was normal.