A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels

Neto, Osório Abath; Silva, Marina Rodrigues e; Martins, Carla Campos; Oliveira, Acary de Souza Bulle; Reed, Umbertina Conti; Biancalana, Valérie; Pesquero, João Bosco; Laporte, Jocelyn; Zanoteli, Edmar

doi:10.1016/j.pediatrneurol.2016.01.023

Cited by 14 publications

(7 citation statements)

References 29 publications

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“…The remaining 2 had movements against gravity and with some resistance. Overall, examination features were consistent with previous reports, 2 , 9 , 11 although we additionally observed neck flexor weakness and the combination of joint hypermobility plus joint contractures in most individuals (figure e-2).…”

Section: Resultssupporting

confidence: 92%

“…Two previous studies examining clinical characteristics were performed in 1999 and 2002, 7 , 8 and each identified considerable disease morbidities and extremely high mortality. The literature also includes several case reports 9 – 11 and a congenital myopathy cohort study (including 8 MTM cases), 11 each corroborating the severe weakness and early mortality of patients with MTM. There remains, however, a critical lack of knowledge of the MTM disease process, limiting the ability to develop outcome measures and hindering current clinical care, particularly as it relates to anticipatory guidance and disease prognostication.…”

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confidence: 96%

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A natural history study of X-linked myotubular myopathy

Amburgey¹,

Tsuchiya

Chastonay

et al. 2017

Neurology

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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.

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Section: Resultssupporting

confidence: 92%

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confidence: 96%

A natural history study of X-linked myotubular myopathy

Amburgey¹,

Tsuchiya

Chastonay

et al. 2017

Neurology

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“…To put our findings in the context of the overall Brazilian population, the nation-wide census conducted in 2019–2020 estimated a total population of 215,786,498 with 2,728,273 live births, of which 1,371,445 were live male births [ 31 ]. Our finding of 21 suspected severe XLMTM patients in this population is consistent with another study that used muscle biopsies and genetic test results from two large muscle biopsy banks and a neuromuscular referral clinic in Brazil [ 32 ]. Among 3065 biopsies obtained between 2008 and 2013, 63 reported prominent nuclei centralizations, of which 8 were compatible with XLMTM [ 32 ].…”

Section: Discussionsupporting

confidence: 90%

A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System

Souza,

Haselkorn,

Baima

et al. 2024

Orphanet J Rare Dis

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Background X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital disease, which is not well-defined. To our knowledge, no studies characterizing the XLMTM disease burden have been conducted in Brazil. We identified and described patients with suspected XLMTM using administrative claims data from the Brazilian public healthcare system. Methods Data from 2015 to 2019 were extracted from the DATASUS database. As no XLMTM-specific ICD-10 code was available, a stepwise algorithm was applied to identify patients with suspected XLMTM by selecting male patients with a congenital myopathies code (G71.2), aged < 18 years at index date (first claim of G71.2), with an associated diagnostic procedure (muscle biopsy/genetic test) and without spinal muscular atrophy or Duchenne muscular dystrophy. We attempted to identify patients with suspected severe XLMTM based on use of both respiratory and feeding support, which are nearly universal in the care of XLMTM patients. Analyses were performed for the overall cohort and stratified by age at index date < 5 years old and ≥ 5 years old. Results Of 173 patients with suspected XLMTM identified, 39% were < 5 years old at index date. Nearly all (N = 166) patients (96%) were diagnosed by muscle biopsy (91% of patients < 5 years old and 99% of patients ≥ 5 years old), six (3.5%) were diagnosed by clinical evaluation (8% of patients < 5 years old and 1% of patients ≥ 5 years old), and one was diagnosed by a genetic test. Most patients lived in Brasilia (n = 55), São Paulo (n = 33) and Minas Gerais (n = 27). More than 85% of patients < 5 years old and approximately 75% of patients ≥ 5 years old had physiotherapy at the index date. In both age groups, nearly 50% of patients required hospitalization at some point and 25% required mobility support. Respiratory and feeding support were required for 3% and 12% of patients, respectively, suggesting that between 5 and 21 patients may have had severe XLMTM. Conclusion In this real-world study, genetic testing for XLMTM appears to be underutilized in Brazil and may contribute to underdiagnosis of the disease. Access to diagnosis and care is limited outside of specific regions with specialized clinics and hospitals. Substantial use of healthcare resources included hospitalization, physiotherapy, mobility support, and, to a lesser extent, feeding support and respiratory support.

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“…Long-term survivors are mostly non-ambulant and ventilator and feeding tube-dependent. XLMTM is also characteristically complicated by systemic diseases including genitourinary disorders, liver dysfunction, spherocytosis and bleeding diathesis [ 8 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies

D’Amico

Longo

Fattori

et al. 2021

Orphanet J Rare Dis

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Background X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation. For XLMTM several therapeutic strategies are under investigation including a study of intravenous MTM1 gene transfer using a recombinant AAV8 vector of which has some concerns arises due to hepatotoxicity. Results We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series. Conclusions We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program.

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A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels

Cited by 14 publications

References 29 publications

A natural history study of X-linked myotubular myopathy

A natural history study of X-linked myotubular myopathy

A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System

Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies

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