A natural history study of X-linked myotubular myopathy

Abstract

Objective:To define the natural history of X-linked myotubular myopathy (MTM).Methods:We performed a cross-sectional study that included an online survey (n = 35) and a prospective, 1-year longitudinal investigation using a phone survey (n = 33).Results:We ascertained data from 50 male patients with MTM and performed longitudinal assessments on 33 affected individuals. Consistent with existing knowledge, we found that MTM is a disorder associated with extensive morbidities, including wheelchair (86.7% nonambulant) and ventilator (75% requiring >16 hours of support) dependence. However, unlike previous reports and despite the high burden of disease, mortality was lower than anticipated (approximate rate 10%/y). Seventy-six percent of patients with MTM enrolled (mean age 10 years 11 months) were alive at the end of the study. Nearly all deaths in the study were associated with respiratory failure. In addition, the disease course was more stable than expected, with few adverse events reported during the prospective survey. Few non–muscle-related morbidities were identified, although an unexpectedly high incidence of learning disability (43%) was noted. Conversely, MTM was associated with substantial burdens on patient and caregiver daily living, reflected by missed days of school and lost workdays.Conclusions:MTM is one of the most severe neuromuscular disorders, with affected individuals requiring extensive mechanical interventions for survival. However, among study participants, the disease course was more stable than predicted, with more individuals surviving infancy and early childhood. These data reflect the disease burden of MTM but offer hope in terms of future therapeutic intervention.

Living-donor liver transplantation for liver hemorrhaging due to peliosis hepatis in X-linked myotubular myopathy: Two cases and a literature review

“…Although the major cause of death in MTM has been shown to be respiratory complications, 3 neither of the present recipients had any respiratory complications, receiving some degree of respiratory support. Tracheostomy can also be useful for providing respiratory support in the perioperative period.…”

“…Although previous studies described up to 50% of MTM patients dying in the first year of life and 90% dying by age 10, 2,12 a recent survey showed that the mean survival of MTM patients was 12 years and 2 months, which was longer than the predicted prognosis. 3,13 Furthermore, a longer prognosis was expected because Table 1).…”

“…A recent paper described the natural history of MTM, in which the mean survival of MTM patients was 12 years and 2 months, and the major cause of death was related to respiratory failure. 3 Although liver involvement is uncommon in MTM, massive bleeding due to peliosis hepatis (PH) is the most fatal complication.…”

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.…”

The difficulties and importance of research in rare genetic diseases

“…highlight the importance of performing research on rare genetic diseases . Their retrospective X‐linked myotubular myopathy (XLMTM) study complements a recent natural history study done by the same group . The investigators reviewed 115 medical records of patients with XLMTM to better characterize disease manifestations and examine previous medical management.…”