丙酮酸脱氢酶复合物缺陷Leigh综合征2例临床及PDHA1基因分析

Clinical and PDHA1 gene analysis of Leigh syndrome with pyruvate dehydrogenase complex deficiency in 2 children

目的探讨PDHA1基因突变所致丙酮酸脱氢酶复合物E1α亚单位缺陷Leigh综合征的临床特点及诊断和治疗。方法回顾分析2例因发育落后就诊,磁共振扫描提示Leigh综合征,并经生化代谢及基因检测确诊患儿的临床资料。结果 2例男性患儿分别于1岁1个月、4个月就诊,发育落后,肌张力障碍,肌力低下;头颅磁共振检查发现双侧基底节区对称性损害;血清丙酮酸、乳酸明显增高,血氨基酸及酯酰肉碱谱无异常。基因分析发现2例患儿X染色体PDHA1基因分别存在c.615C>G、c.605A>G错义突变,均为未报道的新突变,证实为丙酮酸脱氢酶复合物E1α亚单位缺陷所致Leigh综合征。结论 PDHA1基因突变患儿临床表现复杂多样,对于不明原因的发育落后儿童,应注意线粒体病的可能,基因检测有助于诊断、治疗及遗传咨询。

Objective To explore the clinical characteristics, diagnosis and treatment of Leigh syndrome with pyruvate dehydrogenase complex E1 α subunit deficiency caused by PDHA1 gene mutation. Method Two boys visited doctors because of psychomotor retardation. Leigh syndrome was suggested by magnetic resonance imaging (MRI) and confirmed by biochemical metabolism and genetic tests. The clinical data were retrospectively analyzed. Results Two boys visited a doctor at the age of 13 month and 4 months respectively for mental retardation, dystonia and muscle weakness at the age of 13 months and 4 months respectively. Brain MRI revealed symmetrical lesions in bilateral basal ganglia. Serum pyruvic acid and lactic acid levels increased significantly, while blood amino acid and acylcarnitine profiles were normal. Genetic analysis revealed missense mutations in the X chromosome PDHA1 gene , c.615C>G and c.605A>G, in the two boys respectively, which were new mutations never reported. Therefore, the two boys were diagnosed with Leigh syndrome caused by pyruvate dehydrogenase complex E1 α subunit deficiency. Conclusion The clinical manifestations of PDHA1 gene mutation in children are complex and varied. The possibility of mitochondrial disease should be considered in children with developmental retardation of unknown cause. Gene detection is helpful for diagnosis, treatment and genetic counseling.