Objective The aim of the study is to explore the clinical and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous pathogenic variants, and to improve clinicians' awareness of the disease.

Methods The proband was a girl of first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay, intellectual disability, developmental retardation after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. The clinical performance, diagnosis, treatment process, and gene characteristics of COXPD21 caused by TARS2 of the case were analyzed, reviewed, and compared with the literature from the CNKI, Wanfang Data, and biomedical literature database (PubMed) until November 2021.

Results The child was diagnosed with COXPD21 after two heterozygous variants in the TARS2 gene were found via whole exome sequencing. One of the variants was c.1679(exon14) A > C (p.Asp560Ala) missense, derived from the mother, and the other was c.1036(exon10)C > T (p.Arg346Cys) missense, derived from the father. The literature was searched and reviewed with the keywords “mitochondrial encephalomyopathy,” “TARS2,” and “combination oxidative phosphorylation deficiency type 21.” A total of four complete domestic and foreign cases were collected from the literature search.

Conclusion COXPD21 onset by a complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported in China and abroad.

目的 探讨TARS2复合杂合性致病变异所致联合氧化磷酸化缺陷21型（COXPD21）的临床及遗传特征，提高临床医生对该病的认识。

方法 先证者为初生女孩，以反复难治性低钾血症、听力障碍、发育迟缓、智力障碍、感染后发育迟缓、四肢肌张力高、血清乳酸升高为临床表型。对病例的临床表现、诊断、治疗过程以及TARS2引起的COXPD21基因特征进行分析、回顾，并与CNKI、万方数据、生物医学文献数据库（PubMed）截至2021年11月的文献进行比较。

结果 全外显子组测序发现 TARS2 基因两个杂合变异，患儿被诊断为 COXPD21。其中一个变体是 c.1679(exon14) A > C (p.Asp560Ala) 错义，源自母亲，另一个变体是 c.1036(exon10)C > T (p.Arg346Cys) 错义，源自父亲。使用关键词“线粒体脑肌病”、“TARS2”和“组合氧化磷酸化缺陷21型”对文献进行检索和综述。通过文献检索共收集到4个完整的国内外案例。

结论 TARS2复杂杂合变异体COXPD21引发难治性低钾血症，国内外报道较少。