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The Influence of Patient-Reported Joint Manifestations on Quality of Life in Fabry Patients

  • Alexandra Ivleva
  • Ekaterina Weith
  • Atul Mehta
  • Derralynn A. HughesEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 41)

Abstract

Fabry disease, a lysosomal storage disorder, is a rare inborn error of metabolism caused by deficiency of the enzyme alpha galactosidase A and resulting accumulation of globotriaosylceramide. The symptoms of Fabry disease are heterogeneous including renal failure, cardiac hypertrophy, and stroke and may not be well recognized by non-specialist physicians. Patients with milder, later onset of disease often have a delay in diagnosis.

Fabry patients may suffer significant neuropathic pain in the extremities (acroparasthesia) but the degree to which musculoskeletal symptoms contribute to total pain and disability is unknown. Here, we present a questionnaire study focusing on joint manifestations and their impact on daily life of patients with Fabry disease.

Seventy-seven patients with Fabry disease and age-matched healthy controls (49 female and 28 male) took part in a survey focused on joint problems, pain, disability, and quality of life. Joint pain and swelling were reported by 43% of male and 39% of female Fabry patients. Analysis by age group showed higher prevalence of joint problems and decreased quality of life, in terms of mobility, activity, pain, and anxiety, in Fabry patients younger than 50 years compared to healthy controls. Female Fabry patients had higher fatigue scores compared to control subjects. Fabry patients reported problems with vigorous daily activities and gripping.

Musculoskeletal symptoms are common in Fabry patients and contribute to overall pain and decreased quality of life. Awareness of Fabry disease by physicians may be raised to ensure timely diagnosis of this rare disease.

Keywords

Fabry disease Joints manifestations Lysosomal storage disorder Multidisciplinary team-care Musculoskeletal symptoms Patient-reported outcomes 

Notes

Acknowledgments

We are thankful to the patients and control subjects for participation in the survey. The authors acknowledge Royal Free Hospital Research Nurses Capt. Alan Milligan and Mrs. Linda Richfield for their help in patients study enrolment and work with patient records; as well as Mr. Andrew Burgess for critical review on statistical evaluations.

Supplementary material

472895_1_En_84_MOESM1_ESM.zip (94 kb)
Fig. S1 Scatterplots of fatigue scores for Fabry patients and healthy controls. Upper graph displays data on females, lower graph on males (TIFF 114 kb)
472895_1_En_84_MOESM2_ESM.docx (18 kb)
Response to Reveiwers Comments R2 (DOCX 17 kb)

References

  1. Amann-Vesti BR, Gitzelmann G, Widmer U et al (2003) Severe lymphatic microangiopathy in Fabry disease. Lymphat Res Biol 1(3):185–189CrossRefGoogle Scholar
  2. Arends M, Körver S, Hughes DA et al (2017) Phenotype, disease severity and pain are major determinants of quality of life in Fabry disease: results from a large multicenter cohort study. J Inherit Metab Dis.  https://doi.org/10.1007/s10545-017-0095-6. Epub ahead of print
  3. Banikazemi M, Bultas J, Waldek S et al (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146:77–86CrossRefGoogle Scholar
  4. Brady RO, Gal AE, Bradley RM et al (1967) Enzymatic defect in Fabry’s disease: ceramide-trihexosidase deficiency. N Engl J Med 276:1163–1167CrossRefGoogle Scholar
  5. Cimaz R, Guillaume S, Hilz MJ (2011) Awareness of Fabry disease among rheumatologists – current status and perspectives. Clin Rheumatol 30:467–475CrossRefGoogle Scholar
  6. Cole AL, Lee PJ, Hughes DA et al (2007) Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis 30(6):943–951CrossRefGoogle Scholar
  7. Colombi A, Kostyal A, Bracher R et al (1967) Angiokeratoma corporis diffusum – Fabry’s disease. Helv Med Acta 34:67–83PubMedGoogle Scholar
  8. Deegan PB, Baehner AF, Barba Romero MA et al (2006) Natural history of Fabry disease in females in the Fabry outcome survey. J Med Genet 43:347–352CrossRefGoogle Scholar
  9. Desnick RJ, Ioannou YA, Eng CM (2001) α-Galactosidase a deficiency: Fabry disease. In: Scriver CR (ed) The metabolic and molecular bases of inherited disease. McGraw Hill, New York, NY, pp 3733–3774Google Scholar
  10. Germain DP, Waldek S, Banikazemi M et al (2007) Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 18:1547–1557CrossRefGoogle Scholar
  11. Gupta S, Ries M, Kotsopoulos S et al (2005) The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 84:261–268CrossRefGoogle Scholar
  12. Hopkin RJ, Bissler J, Banikazemi M et al (2008) Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry. Pediatr Res 64:550–555CrossRefGoogle Scholar
  13. Kolodny EH, Pastores GM (2002) Anderson-Fabry disease: extrarenal, neurologic manifestations. J Am Soc Nephrol 13(Suppl 2):S150–S153CrossRefGoogle Scholar
  14. Lidove O, Zeller V, Chicheportiche V et al (2016) Musculoskeletal manifestations of Fabry disease: a retrospective study. Joint Bone Spine 83(4):421–426CrossRefGoogle Scholar
  15. Lien YH, Lai LW (2005) Bilateral femoral head and distal tibial osteonecrosis in a patient with Fabry disease. Am J Orthop (Belle Mead NJ) 34(4):192–194Google Scholar
  16. MacDermot KD, Holmes A, Miners AH (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38:769–775CrossRefGoogle Scholar
  17. Manger B, Mengel E, Schaefer RM (2007) Rheumatologic aspects of lysosomal storage diseases. Clin Rheumatol 26:335–341CrossRefGoogle Scholar
  18. 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 Investig 34(3):236–242CrossRefGoogle Scholar
  19. Mersebach H, Johansson JO, Rasmussen AK et al (2007) Osteopenia: a common aspect of Fabry disease. Predictors of bone mineral density. Genet Med 9(12):812–818CrossRefGoogle Scholar
  20. Morgan SH, Crawfurd MA (1988) Anderson-Fabry disease. BMJ 297:872–873CrossRefGoogle Scholar
  21. Nakao S, Takenaka T, Maeda M et al (1995) An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. N Engl J Med 333:288–293CrossRefGoogle Scholar
  22. NHS Digital (2015) National Statistics. Health Survey for England, 2014. http://content.digital.nhs.uk/catalogue/PUB19295
  23. Paira SO, Roverano S, Iribas JL et al (1992) Joint manifestations of Fabry’s disease. Clin Rheumatol 11(4):562–565CrossRefGoogle Scholar
  24. Ross G, Kuwamura F, Goral A (1993) Association of Fabry’s disease with femoral head avascular necrosis. Orthopedics 16(4):471–473PubMedGoogle Scholar
  25. Sadek J, Shellhaas R, Camfield CS et al (2004) Psychiatric findings in four female carriers of Fabry disease. Psychiatr Genet 14(4):199–201CrossRefGoogle Scholar
  26. Schiffmann R, Askari H, Timmons M et al (2007) Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol 18:1576–1583CrossRefGoogle Scholar
  27. Shelley ED, Shelley WB, Kurczynski TW (1995) Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. Pediatr Dermatol 12:215–219CrossRefGoogle Scholar
  28. Sims K, Politei J, Banikazemi M et al (2009) Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events. Natural history data from the Fabry Registry. Stroke 40:788–794CrossRefGoogle Scholar
  29. 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
  30. Wang RY, Lelis A, Mirocha J et al (2007) Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 9:34–45CrossRefGoogle Scholar
  31. Weidemann F, Niemann M, Breunig F et al (2009) Long-term effects of enzyme replacement therapy on Fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 119:524–529CrossRefGoogle Scholar
  32. Whybra C, Kampmann C, Krummenauer F et al (2004) The Mainz severity score index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet 65:299–307CrossRefGoogle Scholar
  33. Wilcox WR, Oliveira JP, Hopkin RJ et al (2008) Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 93:112–128CrossRefGoogle Scholar
  34. Yoshitama T, Nakao S, Takenaka T et al (2001) Molecular genetic, biochemical, and clinical studies in three families with cardiac Fabry’s disease. Am J Cardiol 87:71–75CrossRefGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Alexandra Ivleva
    • 1
  • Ekaterina Weith
    • 2
  • Atul Mehta
    • 3
    • 4
  • Derralynn A. Hughes
    • 3
    • 4
    • 5
    Email author
  1. 1.Welsh School of PharmacyCardiff UniversityCardiffUK
  2. 2.Independent ResearcherBerlinGermany
  3. 3.Lysosomal Storage Disorders UnitLondonUK
  4. 4.Royal Free London NHS Foundation TrustLondonUK
  5. 5.University College LondonLondonUK

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