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Arch Dis Child. 2019 Sep 4. pii: archdischild-2019-317910. doi: 10.1136/archdischild-2019-317910. [Epub ahead of print]

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

Author information

1
Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA beggs@enders.tch.harvard.edu robert.graham@childrens.harvard.edu.
2
The Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
3
Royal Manchester Children's Hospital, Manchester, UK.
4
Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
6
Children's Hospital Colorado, Aurora, Colorado, USA.
7
Children's Research Institute, University of Florida, Gainesville, Florida, USA.
8
Audentes Therapeutics, San Francisco, California, USA.
9
Cure CMD, Torrance, California, USA.
10
Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
11
EpiMetrix, Los Altos, California, USA.
12
Chestnut Medical Communications, Walpole, Massachusetts, USA.
13
Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA beggs@enders.tch.harvard.edu robert.graham@childrens.harvard.edu.

Abstract

PURPOSE:

Individuals with X-linked myotubular myopathy (XLMTM) who survive infancy require extensive supportive care, including ventilator assistance, wheelchairs and feeding tubes. Half die before 18 months of age. We explored respiratory support and associated mortality risk in RECENSUS, particularly among patients ≤5 years old who received respiratory support at birth; this subgroup closely matches patients in the ASPIRO trial of gene therapy for XLMTM.

DESIGN:

RECENSUS is an international, retrospective study of patients with XLMTM. Descriptive and time-to-event analyses examined survival on the basis of age, respiratory support, tracheostomy use, predicted mutational effects and life-sustaining care.

RESULTS:

Outcomes for 145 patients were evaluated. Among 126 patients with respiratory support at birth, mortality was 47% overall and 59% among those ≤5 years old. Median survival time was shorter for patients ≤5 years old than for those >5 years old (2.2 years (IQR 0.7-5.6) vs 30.2 years (IQR 19.4-30.2)). The most common cause of death was respiratory failure (66.7%). Median survival time was longer for patients with a tracheostomy than for those without (22.8 years (IQR 8.7-30.2) vs 1.8 years (IQR 0.2-not estimable)). The proportion of patients living without a tracheostomy was 50% at age 6 months and 28% at age 2 years. Median survival time was longer with provision of life-sustaining care than without (19.4 years (IQR 3.1-not estimable) vs 0.2 years (IQR 0.1-2.1)).

CONCLUSIONS:

High mortality, principally due to respiratory failure, among patients with XLMTM ≤5 years old despite respiratory support underscores the need for early diagnosis, informed decision-making and disease-modifying therapies.

TRIAL REGISTRATION NUMBER:

NCT02231697.

KEYWORDS:

X-linked myotubular myopathy; centronuclear myopathy; congenital myopathy; mortality; respiratory support; retrospective chart review; tracheostomy

Conflict of interest statement

Competing interests: RJG, IH, MLY, NLK and SWY report no conflicts of interest with respect to this study. RJG is an unpaid member of Audentes Therapeutics Board of Scientific and Clinical Advisors. RA is a volunteer for Cure CMD and has no financial interest in Audentes or related to this study. LBL received financial compensation for medical writing, and TH is a consultant to Audentes Therapeutics. ESJ, MN, SR and SP are employees and shareholders of Audentes Therapeutics. AHB is a member of the Audentes Therapeutics Board of Scientific and Clinical Advisors and has received support from a sponsored research agreement with Audentes Therapeutics to cover running costs for this study.

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