A multicenter, retrospective medical record review of X‐linked myotubular myopathy: The recensus study

Abstract

Introduction: X‐linked myotubular myopathy (XLMTM), characterized by severe hypotonia, weakness, respiratory distress, and early mortality, is rare and natural history studies are few. Methods: RECENSUS is a multicenter chart review of male XLMTM patients characterizing disease burden and unmet medical needs. Data were collected between September 2014 and June 2016. Results: Analysis included 112 patients at six clinical sites. Most recent patient age recorded was ≤18 months for 40 patients and >18 months for 72 patients. Mean (SD) age at diagnosis was 3.7 (3.7) months and 54.3 (77.1) months, respectively. Mortality was 44% (64% ≤18 months; 32% >18 months). Premature delivery occurred in 34/110 (31%) births. Nearly all patients (90%) required respiratory support at birth. In the first year of life, patients underwent an average of 3.7 surgeries and spent 35% of the year in the hospital. Discussion: XLMTM is associated with high mortality, disease burden, and healthcare utilization. Muscle Nerve 57: 550–560, 2018

Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis

“…Nearly half die by 18 months of age from respiratory failure or related complications, such as pneumonia, respiratory tract infections or ventilator-related accidents 6–8. Most who survive infancy require mechanical ventilation and supplementary feeding, rely on wheelchairs for mobility, undergo multiple surgeries in their first year of life and die in early childhood 9 10. Those who survive face substantial physical, emotional and financial demands related to their reliance on life-sustaining ventilatory and other forms of support 11–13…”

“…RECENSUS (Audentes Therapeutics, San Francisco, California) is a large, retrospective, multicentre, medical chart review whose aim is to characterise the XLMTM disease manifestations and medical management. Initial analyses demonstrated substantial disease burden, including respiratory support at birth for 90% of patients, 24-hour ventilator dependence for 48%, tracheostomy for 60%, and high rates of hospitalisation and surgical intervention in the first year of life 10. The current analysis explores respiratory support in relation to associated risk of mortality among an expanded cohort of patients who received respiratory support at birth, and the subgroup of patients that most closely matches patients in the INCEPTUS longitudinal, run-in study (NCT02704273) and ASPIRO clinical trial (ie, children ≤5 years receiving respiratory support at birth).…”

AAV-mediated gene transfer restores a normal muscle transcriptome in a canine model of X-linked myotubular myopathy

“…XLMTM is a centronuclear myopathy caused by mutations in the MTM1 gene, coding for the myotubularin protein (Laporte, Hu et al, 1996). Patients exhibit severe muscle weakness, breathing difficulties, and a median survival of 1-2 years (Beggs, Byrne et al, 2018). XLMTM muscle cells have smaller diameters, an abnormal architecture, and a poor excitation-contraction coupling (ECC) capacity (Al-Qusairi, Weiss et al, 2009, Kutchukian, Lo Scrudato et al, 2016, Lawlor, Beggs et al, 2016, Shichiji, Biancalana et al, 2013.…”

X‐linked myotubular myopathy and pulmonary blebs: Not just a muscle disorder

“…In XLMTM, resultant lack or dysfunction of the myotubularin protein leads to severe, progressive skeletal myopathy . Affected boys experience respiratory failure and dysphagia and aspiration risk in early infancy, often requiring mechanical ventilation and feeding tubes . Neuromuscular weakness contributes to cumulative morbidities throughout childhood as well as high mortality rates from respiratory events.…”