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Sleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease

  • Andrew TalbotEmail author
  • Gary Hammerschlag
  • Jeremy Goldin
  • Kathy Nicholls
Research Report
Part of the JIMD Reports book series (JIMD, volume 31)

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.

Keywords

Abnormal periodic leg movements Fabry disease Polysomnography Sleep apnoea Sleep disorder 

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

Notes

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.

References

  1. Baran AS, Richert AC, Douglass AB, May W, Ansarin K (2003) Change in periodic limb movement index during treatment of obstructive sleep apnoea with continuous positive airway pressure. Sleep 26(6):717–720PubMedGoogle Scholar
  2. Becker PM, Novak M (2014) Diagnosis, comorbidities, and management of restless legs syndrome. Curr Med Res Opin 30(8):1441–1460CrossRefPubMedGoogle Scholar
  3. Berry RB, Budhiraja R, Gottlieb DJ et al (2012) Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. J Clin Sleep Med 8(5):597–619PubMedPubMedCentralGoogle Scholar
  4. Bolsover FE, Murphy E, Cipolotti L, Werring DJ, Lachmann RH (2014) Cognitive dysfunction and depression in Fabry disease: a systematic review. J Inherit Metab Dis 27:177–187CrossRefGoogle Scholar
  5. Cox-Brinkman J, Vedder A, Hollak C et al (2007) Three dimensional face shape in Fabry disease. Eur J Hum Genet 15:535–542CrossRefPubMedGoogle Scholar
  6. Desnick RJ, Brady R, Barranger J et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138:338–346CrossRefPubMedGoogle Scholar
  7. Dominguez RO, Michref A, Tanus E, Amartino H (2007) Restless legs syndrome in Fabry disease: clinical feature associated to neuropathic pain is overlooked. Rev Neurol 45(8):474–478PubMedGoogle Scholar
  8. Duning T, Deppe M, Keller S et al (2009) Excessive daytime sleepiness is a common symptom in Fabry disease. Case Rep Neurol 1:33–40CrossRefPubMedPubMedCentralGoogle Scholar
  9. Duning T, Deppe M, Brand E et al (2013) Brainstem involvement as a cause of central sleep apnea: pattern of microstructural cerebral damage in patients with cerebral microangiopathy. PLoS One 8(4):e60304CrossRefPubMedPubMedCentralGoogle Scholar
  10. Earley CJ, Silber MH (2014) Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med 11:807–815CrossRefGoogle Scholar
  11. Epstein LJ, Kristo D, Strollo PJ et al (2009) Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 5(3):263–276PubMedGoogle Scholar
  12. Ferini-Strambi L, Walters AS, Sica D (2014) The relationship among restless legs syndrome (Willis–Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease. J Neurol 261:1051–1068CrossRefPubMedGoogle Scholar
  13. Franzen D, Krayenbuehl PA, Lidove O, Aubert J-A, Barbey F (2013) Pulmonary involvement in Fabry disease: overview and perspectives. Eur J Intern Med 24:707–713CrossRefPubMedGoogle Scholar
  14. Germain DP (2010) Fabry disease. Orphanet J Rare Dis 5:30CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hogarth V, Hughes D, Orteu CH (2012) Pseudoacromegalic facial features in Fabry disease. Clin Exp Dermatol 38:137–139CrossRefPubMedGoogle Scholar
  16. International Restless Leg Syndrome Study Group. Revised IRLSSG diagnostic criteria for RLS 2012. http://irlssg.org/diagnosric-criteria. Last accessed 19 Jan 2016
  17. Johns MW (1992) A new method for measuring daytime sleepiness. The Epworth sleepiness scale. Sleep 14:540–545CrossRefGoogle Scholar
  18. Kim W, Pyeritz RE, Bernhardt BA, Casey M, Litt HI (2007) Pulmonary manifestations of Fabry disease and positive response to enzyme replacement therapy. Am J Med Genet 143:377–381CrossRefPubMedGoogle Scholar
  19. Lang RM, Bierig M, Devereux RB et al (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18:1440–1463CrossRefPubMedGoogle Scholar
  20. Lobo T, Morgan J, Bjorksten A et al (2008) Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement. Intern Med 38:407–414CrossRefGoogle Scholar
  21. Magage S, Lubanda JC, Susa Z et al (2007) Natural history of the respiratory involvement in Anderson-Fabry disease. J Inherit Metab Dis 30:790–799CrossRefPubMedGoogle Scholar
  22. Mehta A, Ricci R, Widmer U et al (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34(3):236–242CrossRefPubMedGoogle Scholar
  23. Mehta A, Clarke JT, Giugliani R et al (2009) Natural course of Fabry disease: changing pattern of causes of death in FOS Outcome Survey. J Med Genet 46:548–552CrossRefPubMedGoogle Scholar
  24. Raiman JAJ, Clarke TM (2010) Pulmonary, ear and less commonly appreciated manifestations (Chap. 18). In: Elstein D (ed) Fabry disease. Springer, New YorkGoogle Scholar
  25. Ries M, Moore DF, Robinson CJ et al (2006) Quantitative dysmorphology assessment in Fabry disease. Genet Med 8(2):96–101CrossRefPubMedGoogle Scholar
  26. Rosenberg DM, Ferrans VJ, Fulmer JD et al (1980) Chronic airflow obstruction in Fabry’s disease. Am J Med 68(6):898–905CrossRefPubMedGoogle Scholar
  27. Somers VK, White DP, Amin R et al (2008) Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118:1080–1111CrossRefPubMedGoogle Scholar
  28. von Scheidt W, Eng CM, Fitzmaurice TF et al (1991) An atypical variant of Fabry’s disease with manifestations confined to the myocardium. N Engl J Med 324:395–399CrossRefGoogle Scholar
  29. Wang RY, Abe JT, Cohen AH, Wilcox WR (2008) Enzyme replacement therapy stabilizes obstructive pulmonary Fabry disease associated with respiratory globotriaosylceramide storage. J Inherit Metab Dis 31:S369–S374CrossRefPubMedGoogle Scholar
  30. Winkelman JW, Gagnon A, Clair AG (2013) Sensory symptoms in restless legs syndrome: the enigma of pain. Sleep Med 14:934–942CrossRefPubMedGoogle Scholar
  31. Zarate YA, Hopkin RJ (2008) Lysosomal storage disease 3: Fabry’s disease. Lancet 372:1427–1435CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Andrew Talbot
    • 1
    Email author
  • Gary Hammerschlag
    • 2
  • Jeremy Goldin
    • 2
    • 3
  • Kathy Nicholls
    • 1
    • 3
  1. 1.Department of Nephrology RadiologyRoyal Melbourne HospitalMelbourneAustralia
  2. 2.Departments of Respiratory and Sleep MedicineRoyal Melbourne HospitalMelbourneAustralia
  3. 3.Department of MedicineUniversity of MelbourneMelbourneAustralia

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