Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease
Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease
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DOI：
10.1542/peds.2004-0718
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发表时间：
2004-10-01
期刊：
影响因子：
8
通讯作者：
Vogel, H
中科院分区：
文献类型：
--
作者：
Scaglia, F;Towbin, JA;Vogel, H
目标。本研究的目的是阐明儿童线粒体疾病的主要临床表现的频率，并根据其临床特征确定其临床病程、预后和生存率。我们对400名被推荐进行线粒体疾病评估的患者的医疗记录进行了回顾。通过使用修订的Walker标准，只有被指定为明确诊断的患者才包括在研究中。共有113名患有线粒体疾病的儿童患者被确认。作为诊断检查的一部分，共有102名(90%)患者接受了肌肉活组织检查。根据诊断标准，在接受评估的患者中，71%的患者发现明显的呼吸链(RC)缺陷。在这个队列中，复合体I缺陷(32%)和复合体I、III和IV缺陷(26%)是最常见的RC缺陷原因，其次是复合体IV(19%)、复合体III(16%)和复合体II缺陷(7%)。病理性线粒体DNA异常率为11.5%。通过多普勒超声心动图诊断，线粒体疾病患者中有相当一部分(40%)表现为心脏病；然而，大多数患者(60%)有主要的神经肌肉表现。未观察到RC缺陷的类型与临床表现之间的相关性。总体而言，分娩时的平均年龄为40个月。然而，心脏病组的平均年龄为33个月，非心脏病组的平均年龄为44个月。心脏病组中26例(58%)表现为肥厚型心肌病，29%表现为扩张型心肌病，其余(13%)表现为左室压实不全。心肌病患者在16岁时存活率为18%。有神经肌肉特征但无心肌病的患者在相同年龄段的存活率为95%。这项研究有力地支持了这一观点，即在RC缺陷患者中，心肌病比之前认为的更常见，并倾向于遵循不同的和更严重的临床过程。尽管线粒体DNA突变的频率比以前报道的要高，但在少数患者中发现了线粒体DNA突变，强调了大多数儿童线粒体疾病遵循孟德尔式的遗传模式。
Objectives. The aim of this study was to elucidate the frequency of major clinical manifestations in children with mitochondrial disease and establish their clinical course, prognosis, and rates of survival depending on their clinical features.Methods. We performed a retrospective review of the medical records of 400 patients who were referred for evaluation of mitochondrial disease. By use of the modified Walker criteria, only patients who were assigned a definite diagnosis were included in the study.Results. A total of 113 pediatric patients with mitochondrial disease were identified. A total of 102 (90%) patients underwent a muscle biopsy as part of the diagnostic workup. A significant respiratory chain ( RC) defect, according to the diagnostic criteria, was found in 71% of the patients who were evaluated. In this cohort, complex I deficiency (32%) and combined complex I, III, and IV deficiencies (26%) were the most common causes of RC defects, followed by complex IV (19%), complex III (16%), and complex II deficiencies (7%). Pathogenic mitochondrial DNA abnormalities were found in 11.5% of the patients. A substantial fraction (40%) of patients with mitochondrial disorders exhibited cardiac disease, diagnosed by Doppler echocardiography; however, the majority (60%) of patients had predominant neuromuscular manifestations. No correlation between the type of RC defect and the clinical presentation was observed. Overall, the mean age at presentation was 40 months. However, the mean age at presentation was 33 months in the cardiac group and 44 months in the noncardiac group. Twenty-six (58%) patients in the cardiac group exhibited hypertrophic cardiomyopathy, 29% had dilated cardiomyopathy, and the remainder (13%) had left ventricular noncompaction. Patients with cardiomyopathy had an 18% survival rate at 16 years of age. Patients with neuromuscular features but no cardiomyopathy had a 95% survival at the same age.Conclusions. This study gives strong support to the view that in patients with RC defects, cardiomyopathy is more common than previously thought and tends to follow a different and more severe clinical course. Although with a greater frequency than previously reported, mitochondrial DNA mutations were found in a minority of patients, emphasizing that most mitochondrial disorders of childhood follow a Mendelian pattern of inheritance.