Natural history of type a Niemann-Pick disease - Possible endpoints for therapeutic trials
Natural history of type a Niemann-Pick disease - Possible endpoints for therapeutic trials
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DOI：
10.1212/01.wnl.0000194208.08904.0c
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发表时间：
2006-01-24
期刊：
影响因子：
9.9
通讯作者：
Wasserstein, MP
中科院分区：
文献类型：
--
作者：
McGovern, MM;Aron, A;Wasserstein, MP
目的：描述A型尼曼-匹克病（NPD）的病程和自然史。研究方法：对10例NPD-A患者（6例男性，4例女性;入组时年龄范围：3至6个月）进行了系列评价，包括临床神经学、眼科和体格检查以及发育评估。还进行了实验室分析、腹部和脑部超声波检查以及胸部X光片检查，并收集了关于并发疾病和死亡原因的信息。结果：所有受影响的婴儿都有正常的新生儿病程和早期发育。所有患者的首发症状均为肝脾肿大。适应性行为的发育年龄不超过10个月，表达性语言的发育年龄不超过12个月，大运动技能的发育年龄不超过9个月，精细运动技能的发育年龄不超过10个月。非神经系统症状包括频繁呕吐、发育不良、呼吸道感染、易怒和睡眠障碍。大多数患者在就诊时神经系统检查正常。后来的神经系统检查显示进行性肌张力减退伴深腱反射丧失。所有患者在12个月时都有樱桃红斑点。从诊断到死亡的中位时间为21个月。9名患者的死亡原因是呼吸衰竭，第10名患者是出血并发症。结论：A型尼曼-匹克病的临床病程在受影响的患者中是相似的，其特征在于通常在3年内导致死亡的无情的神经退行性病程。
Objective: To describe the disease course and natural history of Type A Niemann-Pick disease (NPD). Methods: Ten patients with NPD-A (six male, four female; age range at entry: 3 to 6 months) were serially evaluated including clinical neurologic, ophthalmologic, and physical examinations, and assessment of development. Laboratory analyses, abdominal and brain ultrasounds, and chest radiographs also were obtained and information on intercurrent illnesses and cause of mortality was collected. Results: All affected infants had a normal neonatal course and early development. The first symptom detected in all patients was hepatosplenomegaly. Developmental age did not progress beyond 10 months for adaptive behavior, 12 months for expressive language, 9 months for gross motor skills, and 10 months for fine motor skills. Non-neurologic symptoms included frequent vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbance. Neurologic examination at the time of presentation was normal in most patients. Later neurologic examinations revealed progressive hypotonia with loss of the deep tendon reflexes. All patients had cherry red spots by 12 months. The median time from diagnosis to death was 21 months. The cause of death was respiratory failure in nine patients and complications from bleeding in the tenth. Conclusions: The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.