Abstract
Background
Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact.
Purpose
Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab–based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes).
Methods
The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed.
Result
Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending).
Discussion
The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection.
Clinical trial registration number
UMIN000039191, UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr).
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Acknowledgments
The authors thank Prof. Kingman Strohl for the editorial assistance.
Funding
This study is supported by an Investigator-Sponsored Study grant from Sanofi (SGZ-2018-12403).
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Dr. Yamauchi is principal investigator and is responsible for the study concept and design and interpretation of data. Drs. Yamauchi, Nakayama, Shiota, Ohshima, Terada, Nishijima, Tachibana, Kitamura, Oguri, Shirahama, Aoki, Takatani, and Fujita are responsible for the data collection. Dr. Kosuga is responsible for the examination including genetic assay for diagnosis of Pompe disease. Drs. Ishigaki and Sugie are responsible for the clinical assessment and intervention to myopathy as an advisor. Drs. Yagi and Muraki are responsible for the review of PSG at each institute.
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The funder had no role in the study design, data collection and analysis, and decision to publish or preparation of the manuscript.
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Motoo Yamauchi received a research grant from Sanofi KK for this study (SGZ-2018-12403). All the other authors declare that they have no relevant conflict of interest.
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All procedures performed in studies involving human participants are in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Yamauchi, M., Nakayama, H., Shiota, S. et al. Potential patient screening for late-onset Pompe disease in suspected sleep apnea: a rationale and study design for a Prospective Multicenter Observational Cohort Study in Japan (PSSAP-J Study). Sleep Breath 25, 695–704 (2021). https://doi.org/10.1007/s11325-020-02170-6
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DOI: https://doi.org/10.1007/s11325-020-02170-6