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.