关键词: 联合氧化磷酸化缺陷21型； TARS2基因； 线粒体苏氨酰-tRNA合成酶； 全基因组测序； 癫痫

Abstract: Objective To explore the clinical features and molecular genetic characteristics of combined oxidative phosphorylation deficiency- 21 (COXPD 21 ). Method The clinical data of COXPD 21 in a child were retrospectively analyzed and the related literature was reviewed. Results A 6 -month-old boy had developmental retardation. Epilepsy began at 3 months of age and was manifested with focal seizures, spasms, and myoclonus. The convulsions aggravated after respiratory infections, accompanied by comma, cyanosis, breathlessness, low cardiac sound, hepatomegaly, muscular hypertonia of extremities. The laboratory examinations showed diffuse myocardial damage, severe acidosis and hyperlactic acidemia. Whole genome sequencing (WGS) revealed that the proband had compound heterozygous variations in the TARS 2 gene, c. 987 _ 988 insA and c. 470 C>G, both of which were new variations. The child was diagnosed with COXPD 21 and died at the age of 7 months. Conclusions COXPD 21 has an early onset and poor prognosis, and can lead to severe metabolic encephalopathy. It is caused by TARS2 gene variation. This is the first reported case of COXPD 21 confirmed by genetic testing in China.

Key words: combined oxidative phosphorylation deficiency- 21 ; TARS 2 gene; mitochondrial threonyl-tRNA synthetase; whole genome sequencing; epilepsy