Diaphragmatic dysfunction has been reported in congenital myopathies, muscular dystrophies, and occasionally, mitochondrial respiratory chain deficiency. Using a minimally invasive procedure in 3 young girls, 1 with a heteroplasmic MT-CYB mutation and 2 with biallelic pathogenic TK2 variants, we provided functional evidence of diaphragmatic dysfunction with global respiratory muscle weakness in mitochondrial respiratory chain deficiency. Analysis of respiratory muscle performance using esogastric pressures revealed paradoxical breathing and severe global inspiratory and expiratory muscle weakness with a sniff esophageal inspiratory pressure and a gastric pressure during cough averaging 50% and 40% of predicted values, respectively. This diaphragmatic dysfunction was responsible for severe undiagnosed nocturnal hypoventilation, requiring noninvasive ventilation. Our results underline the interest of this minimally invasive procedure for the evaluation of respiratory muscle performance and its potential value for the monitoring of future clinical trials in respiratory chain deficiency.

中文翻译：

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线粒体呼吸链缺陷伴严重肺泡低通气综合征的膈肌功能障碍的证据

在先天性肌病、肌营养不良症和偶尔的线粒体呼吸链缺陷中已经报道了膈肌功能障碍。在 3 名年轻女孩中使用微创手术，其中 1 名具有异质性 MT-CYB 突变，2 名具有双等位基因致病性 TK2 变异，我们提供了线粒体呼吸链缺陷中膈肌功能障碍伴整体呼吸肌无力的功能证据。使用食管胃压力对呼吸肌功能的分析显示，呼吸矛盾和严重的整体吸气和呼气肌无力，呼吸食管吸气压力和咳嗽期间胃压力分别平均为预测值的 50% 和 40%。这种膈肌功能障碍是导致严重未确诊的夜间通气不足的原因，需要无创通气。我们的结果强调了这种微创手术对评估呼吸肌性能的兴趣及其对监测未来呼吸链缺陷临床试验的潜在价值。