The MTM-CNM Liver Collaborative Working Group was initiated in August of 2021 by two patient organizations in the Myotubular and Centronuclear Myopathy community, MTM-CNM Family Connection (US), and Myotubular Trust (UK). The patient organizations launched a joint effort to gather academic researchers and medical experts in the community to seek a better understanding of liver challenges experienced in the community, from both a historical perspective on issues naturally occurring and in the context of emerging clinical trials.

Myotubular and Centronuclear Myopathy (MTM and CNM) have historically been viewed as muscle diseases with significant impact on skeletal muscle. Supportive interventions for respiratory function have been emphasized as a primary, crucial component for successful management of the disease, especially in more severe presentations. Liver issues have been less noted, most likely underreported by individuals, and minimally mentioned in early studies and analyses of the disease. There have been documented rare occurrences of hepatic peliosis, and more commonly mentioned elevation in serum liver enzymes. More recently, there has been an evolving understanding of occurrences of hepatic cholestasis as an additional liver-related pathology associated with MTM/CNM. Also, within the context of the community’s first two clinical trials, there have been treatment-related adverse events reported in liver function, and within the gene therapy trial four reported deaths related to liver failure. Definitive understanding of potential causality, or correlation with possible underlying pre-existing liver dysfunction, has still not yet been determined, nor yet fully understood.