Morava E, Dinopoulos A, Kroes H Y, Rodenburg R J T, van Bokhoven H, van den Heuvel L P, Smeitink J A M
Nijmegen Center for Mitochondrial Disorders, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
Neuropediatrics. 2005 Jun;36(3):214-7. doi: 10.1055/s-2005-865610.
Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.
乔伯特综合征是一种基因异质性疾病。诊断标准包括发作性换气过度、异常眼球运动、精神运动发育迟缓、肌张力减退、共济失调以及特征性的神经影像学表现（磨牙征）。许多这些临床特征在患有线粒体疾病的新生儿中也有观察到。先天性脑畸形，包括小脑发育不全，已在丙酮酸脱氢酶缺乏症中有所描述。然而，蚓部和小脑脚的畸形以及轴突交叉的缺失是乔伯特综合征的特征，但在患有线粒体疾病的患者中是独特的。在此，我们描述了一名患有乔伯特综合征的儿童，其表现为原发性乳酸性血症、丙酮酸氧化速率降低、ATP生成减少，并且在新鲜肌肉活检中测得丙酮酸脱氢酶复合物活性轻度降低。对PDHc E1α基因和PDHX基因的序列分析未发现突变。该患者通过饲管持续喂养两年，临床症状显著改善，慢性乳酸性血症完全消退。第二次肌肉活检显示丙酮酸氧化速率和ATP生成显著降低，但丙酮酸脱氢酶复合物活性正常。我们认为，我们患者中所描述的线粒体功能障碍是继发于导致乔伯特综合征的潜在突变。
