Chien Yin-Hsiu, Lee Ni-Chung, Thurberg Beth L, Chiang Shu-Chuan, Zhang Xiaokui Kate, Keutzer Joan, Huang Ai-Chu, Wu Mei-Hwan, Huang Pei-Hsin, Tsai Fuu-Jen, Chen Yuan-Tsong, Hwu Wuh-Liang
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan.
Pediatrics. 2009 Dec;124(6):e1116-25. doi: 10.1542/peds.2008-3667.
Pompe disease causes progressive, debilitating, and often life-threatening musculoskeletal, respiratory, and cardiac symptoms. Favorable outcomes with early intravenous enzyme-replacement therapy and alglucosidase alfa have been reported, but early clinical diagnosis before the development of severe symptoms has rarely been possible in infants.
We recently conducted a newborn screening pilot program in Taiwan to improve the early detection of Pompe disease. Six of 206088 newborns screened tested positive and were treated for Pompe disease. Five had the rapidly progressive form of Pompe disease, characterized by cardiac and motor involvement, and were treated soon after diagnosis. The sixth patient was started on treatment at 14 months of age because of progressive muscle weakness. Outcomes were compared with treated patients whose disease was diagnosed clinically and with untreated historical control subjects.
At the time of this report, patients had been treated for 14 to 32 months. The 5 infants who had early cardiac involvement demonstrated normalization of cardiac size and muscle pathology with normal physical growth and age-appropriate gains in motor development. The infant without cardiac involvement also achieved normal motor development with treatment. Survival in patients who had newborn screening was significantly improved compared with those in the untreated reference cohort (P = .001). Survival in the treated clinical comparators was reduced but not statistically different from that in the newborn screening group (P = .48).
Results from this study indicate that early treatment can benefit infants with Pompe disease and highlight the advantages of early diagnosis, which can be achieved by newborn screening.
庞贝病会引发进行性、使人衰弱且往往危及生命的肌肉骨骼、呼吸和心脏症状。已有报道称早期静脉注射酶替代疗法和阿糖苷酶α可带来良好疗效，但婴儿在出现严重症状之前很少能实现早期临床诊断。
我们最近在台湾开展了一项新生儿筛查试点项目，以改善庞贝病的早期检测。在筛查的206088名新生儿中，有6名检测呈阳性并接受了庞贝病治疗。其中5名患有快速进展型庞贝病，其特征为心脏和运动功能受累，在诊断后不久即开始治疗。第六名患者因进行性肌肉无力在14个月大时开始接受治疗。将这些患者的治疗结果与临床诊断疾病的已治疗患者以及未经治疗的历史对照受试者进行比较。
在撰写本报告时，患者已接受治疗14至32个月。5名早期有心脏受累的婴儿心脏大小恢复正常，肌肉病理表现正常，身体正常生长，运动发育达到相应年龄水平。未出现心脏受累的婴儿经治疗后运动发育也正常。与未经治疗的参考队列相比，接受新生儿筛查的患者生存率显著提高（P = 0.001）。接受治疗的临床对照者的生存率有所降低，但与新生儿筛查组相比无统计学差异（P = 0.48）。
本研究结果表明，早期治疗可使庞贝病婴儿受益，并突出了早期诊断的优势，而早期诊断可通过新生儿筛查实现。
