Clinical characteristics and molecular genetic analysis of patients with mitochondrial disease caused by acute central respiratory failure due to mtDNA8344A>G gene mutation / 中华神经科杂志

ABSTRACT

Objective:To summarize the phenotype of mtDNA8344A>G and to explore the new phenotype.Methods:A family with mtDNA 8344A>G was retrospectively analyzed in the Children′s Hospital Affiliated to the Capital Institute of Pediatrics in April 2019. The clinical data of the proband and his mother were collected and summarized.Results:A four-year-old boy presented with rapidly progressing central respiratory failure and continuous mechanical ventilation, whose serum lactate levels fluctuated between 4.5 to 8.3 mmol/L. Linear abnormality signals from dorsal medulla to the first and second cervical spine were displayed on cranial magnetic resonance imaging. Ragged red fiber and ragged broken blue fibers, cytochrome C oxidase negative muscle fibers and enhanced vascular succinate dehydrogenase reaction were seen in muscle biopsy, accorded with the pathological characteristics of mitochondrial myopathy. The activity detection of respiratory chain enzyme complex in muscle tissues showed decreased activity of mitochondrial respiratory chain enzyme complex Ⅰ and complex Ⅳ. mtDNA 8344A>G mutation was detected in his peripheral blood lymphocyte and urine exfoliated epithelial cells. The proportion of mutations in his blood lymphocytes was 77.29%, and the proportion of mutations in his urothelial epithelial cells was 90.13%. His mother was 30 years old, thin in stature without obvious clinical symptoms and signs. The mutant mtDNA 8344A>G was also detected in her peripheral blood and urine. The mutant rate in her blood and urine was 77.29% and 90.13% respectively.Conclusions:A case of rapidly progressive central respiratory failure in children and his family are reported. Genetic testing showed mtDNA8344A>G mutation, and both muscle biopsy pathology and muscle tissue respiratory chain enzyme complex activity test results supported mitochondrial disease. By this case, the phenotype spectrum of the gene was expanded.