Abstract
Objectives: To assess the prevalence of sleep disorder(s) in males with Fabry disease and explore possible association with disease phenotype.
Background: Fabry disease, an X-linked lysosomal storage disease caused by deficiency in α-galactosidase, results in intracellular accumulation of globotriaosylceramide. It causes organ dysfunction, most significantly affecting renal, cerebrovascular and cardiovascular systems. Respiratory involvement may include obstructive lung disease, reduced diffusing capacity and thickened soft and hard palates. Patients commonly develop small-fibre sensory peripheral neuropathy manifested by acroparaesthesia and pain crises. Combined with self-reported sleep disturbance and snoring, these features suggest an increased risk of sleep disorders.
Methods: In-laboratory polysomnography (PSG) studies and sleep inventory assessments, including Epworth Sleepiness Scale (ESS), were performed in a cohort of male Fabry patients. PSGs were reviewed by a sleep physician. Sleep-disordered breathing and periodic leg movements were targeted for analysis. Associations with renal, cardiovascular and cerebrovascular function were sought.
Results: Twenty males underwent overnight PSG. Patient baseline characteristics included age 43.9 ± 10.7 years, BMI 24.3 ± 3.8 kg/m2, neck circumference 39.7 ± 3.3 cm and ESS 9.8 ± 5.1 (7/20, abnormal ESS >10). Abnormal periodic leg movement index (PLMI) was present in 95% (mean frequency 42.4 ± 28.5/min) and sleep-disordered breathing in 50% patients. Periodic leg movements were associated with pain and depression but not with increased cortical arousal.
Conclusions: Sleep-disordered breathing and abnormal PLMI are highly prevalent in patients with FD. The presence of abnormal PLMI alone appears to have minimal impact on sleep disturbance, but is associated with depression and analgesic requirement.
Competing interests: None declared
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Abbreviations
- AHI:
-
Apnoea–hypopnea index
- EEG:
-
Electroencephalogram
- EMG:
-
Electromyogram
- ERT:
-
Enzyme replacement therapy
- FD:
-
Fabry disease
- Gb3:
-
Globotriaosylceramide
- OSA:
-
Obstructive sleep apnoea
- PLMI:
-
Periodic leg movement index
- PSG:
-
Polysomnography
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Acknowledgements
The authors thank Alexander Gorelik for invaluable assistance with statistics, Andrew Perkins for assistance with method preparation and performing sleep studies and Elizabeth Centra and Donna North for assistance with patient support.
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Communicated by: Markus Ries, MD, PhD, MHSc, FCP
Appendices
Take-Home Message
Sleep-disordered breathing and abnormal periodic leg movements are highly prevalent in male Fabry patients and significantly impact on patient well-being.
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Details of Contributions of Individual Authors
Andrew Talbot was primarily responsible for planning the study, patient recruitment and primary data interpretation, including statistical analysis and original manuscript preparation.
Gary Hammerschlag conducted patient data collection, initial sleep study analysis and data interpretation including manuscript editing.
Jeremy Goldin performed sleep study interpretation, data collection and manuscript editing.
Kathy Nicholls contributed to patient recruitment and consent for study, data interpretation and original manuscript preparation.
Conflict of Interest: Nil Direct
Andrew Talbot has received research support, speaker honoraria and travel assistance from Shire Corporation and Sanofi Corporation, speaker honoraria and travel assistance from Dainippon Sumitomo Pharma Co and research support from Amicus Therapeutics and Protalix Biotherapeutics.
Kathy Nicholls has received research support, speaker honoraria and travel assistance from Shire Corporation and Sanofi Corporation and research support from Amicus Therapeutics and Protalix Biotherapeutics.
Gary Hammerschlag declares that he has no conflict of interest relevant to this project.
Jeremy Goldin declares that he has no conflict of interest relevant to this project.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). Informed consent was obtained from all patients for data analysis of results included in the study.
This article does not contain any studies with animal subjects performed by any of the authors.
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Talbot, A., Hammerschlag, G., Goldin, J., Nicholls, K. (2016). Sleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 31. JIMD Reports, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_549
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DOI: https://doi.org/10.1007/8904_2016_549
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