Skip to main content
SpringerLink
Log in

Carpal Tunnel Syndrome in Fabry Disease

  • Case Report
  • Chapter
  • First Online:
JIMD Reports - Case and Research Reports, 2011/2

Part of the book series: JIMD Reports ((JIMD,volume 2))

Abstract

Carpal tunnel syndrome (CTS) is a common peripheral mononeuropathy affecting up to 4% of the general population, typically women in late middle age. The incidence in patients with Fabry disease (FD) is unclear, but may affect 25% of patients with this X-linked lysosomal storage disease. We report three cases of CTS in young Caucasian male patients with classical FD, who developed CTS symptoms with supportive nerve conduction study (NCS) findings. Two patients had bilateral CTS and two had evidence of concurrent ulnar nerve neuropathy on NCS, suggesting a systemic process contributed to nerve compression. All were receiving enzyme replacement therapy (ERT) and had a moderate burden of FD complications. It is possible that an increase in connective tissue in the intracarpal canal in FD patients may be incited by injury to fibroblasts, via either accumulation of globotriaosylceramide (GL3) or local ischaemia through endothelial injury. The former hypothesis may be a more plausible explanation for the development of CTS, as histology of the flexor retinaculae from our patients has demonstrated fibroblasts with characteristic vacuolation and excessive myxomatous stroma, despite endothelial clearance of GL3 in these patients receiving ERT. CTS should not be overlooked in FD patients and young patients presenting with CTS should be evaluated for an underlying systemic or genetic disorder. Surgical carpal tunnel decompression was effective in our patients, already troubled by long-standing acroparesthesia, in providing sustained relief of symptoms.

Competing interests: None declared.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Askari H, Kaneski CR, Semino-Mora C, Desai P, Ang A, Kleiner DE, Perlee LT, Quezado M, Spollen LE, Wustman BA, Schiffmann R (2007) Cellular and tissue localization of globotriaosylceramide in Fabry disease. Virchows Arch 451(4):823–834

    Article  PubMed  CAS  Google Scholar 

  • Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosen I (1999) Prevalence of carpal tunnel syndrome in a general population. JAMA 282(2):153–158

    Article  PubMed  CAS  Google Scholar 

  • Beck M (2006) The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease. Acta Paediatr Suppl 95(451):43–46

    Article  PubMed  Google Scholar 

  • Bland JD (2000) A neurophysiological grading scale for carpal tunnel syndrome. Muscle Nerve 23(8):1280–1283

    Article  PubMed  CAS  Google Scholar 

  • Charles J, Fahridin S, Britt H (2009) Carpal tunnel syndrome. Aust Fam Physician 38(9):665

    PubMed  Google Scholar 

  • Elleder M (2003) Sequelae of storage in Fabry disease – pathology and comparison with other lysosomal storage diseases. Acta Paediatr Suppl 92(443):46–53, discussion 45

    PubMed  CAS  Google Scholar 

  • Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ (2001) Safety and efficacy of recombinant human alpha-galactosidase A–replacement therapy in Fabry's disease. N Engl J Med 345(1):9–16

    Article  PubMed  CAS  Google Scholar 

  • Galanos J, Nicholls K, Grigg L, Kiers L, Crawford A, Becker G (2002) Clinical features of Fabry's disease in Australian patients. Intern Med J 32(12):575–584

    Article  PubMed  CAS  Google Scholar 

  • Gelberman RH, Hergenroeder PT, Hargens AR, Lundborg GN, Akeson WH (1981) The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am 63(3):380–383

    PubMed  CAS  Google Scholar 

  • Hakim AJ, Cherkas L, El Zayat S, MacGregor AJ, Spector TD (2002) The genetic contribution to carpal tunnel syndrome in women: a twin study. Arthritis Rheum 47(3):275–279

    Article  PubMed  Google Scholar 

  • Hasholt L, Wandall A, Sorensen SA (1988) Enzyme replacement in Fabry endothelial cells and fibroblasts: uptake experiments and electron microscopical studies. Clin Genet 33(5):360–371

    Article  PubMed  CAS  Google Scholar 

  • Hilz MJ, Stemper B, Kolodny EH (2000) Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain 84(2–3):361–365

    Article  PubMed  CAS  Google Scholar 

  • Hilz MJ, Brys M, Marthol H, Stemper B, Dutsch M (2004) Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology 62(7):1066–1072

    Article  PubMed  CAS  Google Scholar 

  • Kawashima I, Watabe K, Tajima Y, Fukushige T, Kanzaki T, Kanekura T, Sugawara K, Ohyanagi N, Suzuki T, Togawa T, Sakuraba H (2007) Establishment of immortalized Schwann cells from Fabry mice and their low uptake of recombinant alpha-galactosidase. J Hum Genet 52(12):1018–1025

    Article  PubMed  CAS  Google Scholar 

  • Kaye EM, Kolodny EH, Logigian EL, Ullman MD (1988) Nervous system involvement in Fabry's disease: clinicopathological and biochemical correlation. Ann Neurol 23(5):505–509

    Article  PubMed  CAS  Google Scholar 

  • Keslova-Veselikova J, Hulkova H, Dobrovolny R, Asfaw B, Poupetova H, Berna L, Sikora J, Golan L, Ledvinova J, Elleder M (2008) Replacement of alpha-galactosidase A in Fabry disease: effect on fibroblast cultures compared with biopsied tissues of treated patients. Virchows Arch 452(6):651–665

    Article  PubMed  CAS  Google Scholar 

  • Kocen RS, Thomas PK (1970) Peripheral nerve involvement in Fabry's disease. Arch Neurol 22(1):81–88

    Article  PubMed  CAS  Google Scholar 

  • Laaksonen SM, Roytta M, Jaaskelainen SK, Kantola I, Penttinen M, Falck B (2008) Neuropathic symptoms and findings in women with Fabry disease. Clin Neurophysiol 119(6):1365–1372

    Article  PubMed  Google Scholar 

  • Lozano-Calderon S, Anthony S, Ring D (2008) The quality and strength of evidence for etiology: example of carpal tunnel syndrome. J Hand Surg Am 33(4):525–538

    Article  PubMed  Google Scholar 

  • Luciano CA, Russell JW, Banerjee TK, Quirk JM, Scott LJ, Dambrosia JM, Barton NW, Schiffmann R (2002) Physiological characterization of neuropathy in Fabry's disease. Muscle Nerve 26(5):622–629

    Article  PubMed  Google Scholar 

  • Mattioli S, Baldasseroni A, Bovenzi M, Curti S, Cooke RM, Campo G, Barbieri PG, Ghersi R, Broccoli M, Cancellieri MP, Colao AM, Dell'omo M, Fateh-Moghadam P, Franceschini F, Fucksia S, Galli P, Gobba F, Lucchini R, Mandes A, Marras T, Sgarrella C, Borghesi S, Fierro M, Zanardi F, Mancini G, Violante FS (2009) Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study. BMC Public Health 9:343

    Article  PubMed  Google Scholar 

  • Mayes JS, Cray EL, Dell VA, Scheerer JB, Sifers RN (1982) Endocytosis of lysosomal alpha-galactosidase A by cultured fibroblasts from patients with Fabry disease. Am J Hum Genet 34(4):602–610

    PubMed  CAS  Google Scholar 

  • Murray GJ, Anver MR, Kennedy MA, Quirk JM, Schiffmann R (2007) Cellular and tissue distribution of intravenously administered agalsidase alfa. Mol Genet Metab 90(3):307–312

    Article  PubMed  CAS  Google Scholar 

  • Schiffmann R (2006) Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy. Acta Neurol Belg 106(2):61–65

    PubMed  Google Scholar 

  • Sima AA, Robertson DM (1978) Involvement of peripheral nerve and muscle in Fabry's disease. Histologic, ultrastructural, and morphometric studies. Arch Neurol 35(5):291–301

    Article  PubMed  CAS  Google Scholar 

  • Sri-Ram K, Vellodi A, Pitt M, Eastwood DM (2007) Carpal tunnel syndrome in lysosomal storage disorders: simple decompression or external neurolysis? J Pediatr Orthop B 16(3):225–228

    Article  PubMed  Google Scholar 

  • Thurberg BL, Fallon JT, Mitchell R, Aretz T, Gordon RE, O'Callaghan MW (2009) Cardiac microvascular pathology in Fabry disease: evaluation of endomyocardial biopsies before and after enzyme replacement therapy. Circulation 119(19):2561–2567

    Article  PubMed  Google Scholar 

  • Torvin Moller A, Winther Bach F, Feldt-Rasmussen U, Rasmussen A, Hasholt L, Lan H, Sommer C, Kolvraa S, Ballegaard M, Staehelin Jensen T (2009) Functional and structural nerve fiber findings in heterozygote patients with Fabry disease. Pain 145(1–2):237–245

    Article  PubMed  Google Scholar 

  • Toyooka K, Said G (1997) Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's disease. J Neurol 244(7):464–468

    Article  PubMed  CAS  Google Scholar 

  • Uchiyama S, Itsubo T, Nakamura K, Kato H, Yasutomi T, Momose T (2010) Current concepts of carpal tunnel syndrome: pathophysiology, treatment, and evaluation. J Orthop Sci 15(1):1–13

    Article  PubMed  Google Scholar 

  • Van Meir N, De Smet L (2003) Carpal tunnel syndrome in children. Acta Orthop Belg 69(5):387–395

    PubMed  Google Scholar 

  • Werner RA, Andary M (2002) Carpal tunnel syndrome: pathophysiology and clinical neurophysiology. Clin Neurophysiol 113(9):1373–1381

    Article  PubMed  Google Scholar 

  • Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, Desnick RJ, Germain DP (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75(1):65–74

    Article  PubMed  CAS  Google Scholar 

  • Yuen A, Dowling G, Johnstone B, Kornberg A, Coombs C (2007) Carpal tunnel syndrome in children with mucopolysaccaridoses. J Child Neurol 22(3):260–263

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology Department, Royal Melbourne Hospital, 1 South East Outpatient Building, Grattan St, Parkville, 3050, VIC, Australia

    Joanna Ghali & Kathy Nicholls

  2. Department of Anatomical Pathology, Royal Melbourne Hospital, Grattan St, Parkville, 3050, VIC, Australia

    Anand Murugasu

  3. Department of Neurophysiology, Royal Melbourne Hospital, Grattan St, Parkville, 3050, VIC, Australia

    Timothy Day

Authors
  1. Joanna Ghali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anand Murugasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Timothy Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathy Nicholls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joanna Ghali .

Editor information

Editors and Affiliations

    Additional information

    Communicated by: Robin Lachmann.

    Synopsis

    Synopsis

    Carpal tunnel syndrome may be a sequela of classical Fabry Disease (through injury to fibroblasts or local ischaemia within the carpal tunnel) despite long-term enzyme replacement therapy, and effective relief of symptoms can be achieved with surgical decompression.

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2011 SSIEM and Springer-Verlag Berlin Heidelberg

    About this chapter

    Cite this chapter

    Ghali, J., Murugasu, A., Day, T., Nicholls, K. (2011). Carpal Tunnel Syndrome in Fabry Disease. In: JIMD Reports - Case and Research Reports, 2011/2. JIMD Reports, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_37

    Download citation

    • DOI: https://doi.org/10.1007/8904_2011_37

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Publisher Name: Springer, Berlin, Heidelberg

    • Print ISBN: 978-3-642-24757-6

    • Online ISBN: 978-3-642-24758-3

    • eBook Packages: MedicineMedicine (R0)

    Publish with us

    Policies and ethics

    Search

    Navigation