Inoue Kenji, Kato Takeo, Terasaki Eisuke, Ishihara Mariko, Fujii Tatsuya, Aida Yuko, Murayama Kei
Shiga Medical Center for Children, Shiga, Japan.
Department of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Osaka, Japan.
Neuropediatrics. 2025 Feb;56(1):51-55. doi: 10.1055/s-0044-1788333. Epub 2024 Jul 15.
X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy that commonly manifests with liver involvement. In most XLMTM cases, disease-causing variants have been identified in the myotubularin gene () on chromosome Xq28, which encodes myotubularin protein (MTM1). The impairment of mitochondrial respiratory chain (MRC) enzyme activity in muscle has been observed in the XLMTM mouse model. Though several reports mentioned possible mechanisms of liver involvement in XLMTM patients and animal models, the precise underlying mechanisms remain unknown, and there is no report focused on mitochondrial functions in hepatocytes in XLMTM. We encountered two patients with XLMTM who had liver involvement. We measured MRC enzyme activities in two muscle biopsy specimens, and one liver specimen from our patients to investigate whether variants cause MRC dysfunction and whether mitochondrial disturbance is associated with organ dysfunction. MRC enzyme activities decreased in skeletal muscles but were normal in the liver. In our patients, the impaired MRC enzyme activity found in muscle is consistent with previously reported mechanisms that the loss of MTM1-desmin intermediate filament and MTM1-IMMT (a mitochondrial membrane protein) interaction led to the mitochondrial dysfunction. However, our study showed that liver involvement in XLMTM may not be associated with mitochondrial dysfunction.
X连锁性肌管性肌病（XLMTM）是一种罕见的先天性肌病，常伴有肝脏受累。在大多数XLMTM病例中，已在X染色体q28上的肌管素基因（）中鉴定出致病变异，该基因编码肌管素蛋白（MTM1）。在XLMTM小鼠模型中已观察到肌肉中线粒体呼吸链（MRC）酶活性受损。尽管有几份报告提到了XLMTM患者和动物模型中肝脏受累的可能机制，但确切的潜在机制仍然未知，并且没有关于XLMTM患者肝细胞线粒体功能的报告。我们遇到了两名患有XLMTM且伴有肝脏受累的患者。我们测量了两名患者的两份肌肉活检标本以及一份肝脏标本中的MRC酶活性，以研究变异是否会导致MRC功能障碍以及线粒体紊乱是否与器官功能障碍有关。骨骼肌中的MRC酶活性降低，但肝脏中的活性正常。在我们的患者中，肌肉中发现的MRC酶活性受损与先前报道的机制一致，即MTM1 - 结蛋白中间丝和MTM1 - IMMT（一种线粒体膜蛋白）相互作用丧失导致线粒体功能障碍。然而，我们的研究表明，XLMTM中的肝脏受累可能与线粒体功能障碍无关。
