丙酮酸脱氢酶复合物缺乏症1家系2例临床及遗传特点
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南京医科大学附属儿童医院

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LINC00634在儿童癫痫发生发展中的作用及机制研究


Clinical and genetic characteristics of pyruvate dehydrogenase complex deficiency in 2 cases of a family
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    摘要:

    目的 探讨PDHA1基因突变致丙酮酸脱氢酶复合物缺乏症的分子遗传学机制、临床特点、诊断和治疗。方法 对就诊于南京医科大学附属儿童医院神经内科的1家系2例丙酮酸脱氢酶复合物缺乏症患儿进行临床表现、生化检验、影像学特征、治疗效果的分析,应用高通量测序、Sanger测序对其家系进行遗传学分析。结果 例1女性患儿于9岁3月龄就诊,发育迟缓,行走不稳,肌张力低下;头颅核磁共振检查提示两侧小脑、中脑、基底节区及侧脑室旁多发异常信号;血清乳酸及尿丙酮酸明显增高。例2女性患儿(例1胞妹)于2岁0月龄就诊,发育迟缓,惊厥持续状态,肌张力低下;头颅核磁共振检查提示两侧侧脑室旁、基底节区、两侧大脑脚多发异常信号;血清乳酸明显增高。基因检测发现该2例患儿X染色体PDHA1基因均存在c.223G>C错义突变,证实为丙酮酸脱氢酶复合物E1-α亚单位缺陷,并对其父母进行基因验证,其父亲该位点无变异,其母亲同样检出上述基因变异。该位点变异为本研究首次报道。给予维生素B1、辅酶Q10、生酮饮食治疗及康复训练等,随访1年,两例患儿运动与认知功能均有改善。结论 PDHA1基因突变患儿临床表现复杂多样,且女性患者因有X染色体随机失活,更为罕见,对于不明原因的精神运动发育迟缓、高乳酸血症、肌张力低下、癫痫发作儿童,需警惕该病,基因检测有助于及时明确诊断和治疗。

    Abstract:

    Objective: To investigate the molecular genetic mechanism, clinical characteristics, diagnosis and treatment of pyruvate dehydrogenase complex deficiency caused by PDHA1 gene mutation. Methods:Two children with pyruvate dehydrogenase complex deficiency in one family were treated in the Department of Neurology, Children""s Hospital Affiliated to Nanjing Medical University. The clinical manifestations, biochemical tests, imaging features and therapeutic effects were analyzed. The genetic analysis of the family was performed by high-throughput sequencing and Sanger sequencing. Results: Case 1 was diagnosed at 9 years and 3 months old with developmental delay, walking instability and hypotonia. Brain magnetic resonance imaging (MR) showed multiple abnormal signals in the bilateral cerebellum, midbrain, basal ganglia and lateral ventricle.Serum lactic acid and urine pyruvate increased significantly. Case 2 (Case 1 sister) was presented at 2 years old with developmental delay, persistent convulsion, and hypotonia. Brain magnetic resonance imaging (MR) showed multiple abnormal signals in the bilateral periventricular, basal ganglia and bilateral cerebral peduncles. Serum lactic acid increased significantly. The two children were found to have C. 223G>C missense mutation in PDHA1 gene of X chromosome, which was confirmed to be the subunit defect of E1-α complex of pyruvate dehydrogenase. Gene verification was conducted on their parents, and no variation was found in this site in their father, and the above genetic variation was also detected in their mother. This mutation was reported for the first time in this study. Vitamin B1, coenzyme Q10, ketogenic diet and rehabilitation training were given to the two children. After 1 year of follow-up, the motor and cognitive functions of the two children were improved. Conclusion: The clinical manifestations of children with PDHA1 gene mutation are complex and diverse, and the random inactivation of X chromosome in female patients is more rare. For children with unexplained psychomotor retardation, hyperlactacidemia, hypotonia, and epileptic seizure, it is necessary to be vigilant about this disease, and gene detection is helpful for timely diagnosis and treatment.

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  • 收稿日期:2023-02-21
  • 最后修改日期:2023-03-29
  • 录用日期:2023-05-23
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