Journal of Inherited Metabolic Disease

, Volume 29, Issue 5, pp 653–659 | Cite as

Improvement of sympathetic skin responses under enzyme replacement therapy in Fabry disease

  • L. B. Jardim
  • I. Gomes
  • C. B. O. Netto
  • D. B. Nora
  • U. S. Matte
  • F. Pereira
  • M. G. Burin
  • L. Kalakun
  • R. Giugliani
  • J. Becker
Original Article

Summary

Aim To report the effect of enzyme replacement therapy (ERT) in sympathetic skin responses (SSR) of patients with Fabry disease. Patients and methods Seven male patients were included in an open-label protocol using agalsidase-alfa, continued at regular intervals. Five patients completed 24 months of ERT and two of them completed 18 months. Two main measurements were performed at baseline, as well as 1 and 2 years after ERT: (1) a standard neurological examination (NE), with a detailed evaluation of the sensory perception of light touch, pinprick, cold, hot, and vibratory stimuli; (2) the SSR amplitudes. Results Although there were no significant differences between NE in this time period, all patients reported general improvement in their subjective reports of acroparaesthesia and sweating. Before starting ERT, the SSR amplitudes were either too small (3/7 patients) or absent (4/7 patients): the average (range) amplitude of 122 μV (0 through 492) was statistically smaller than that found in a control group, i.e. 1453.6 μV (619.7–2754) (p<0.0001, t-test). Mean ± SD SSR amplitude increased to 1088± 690 μV in the second year of ERT, reaching the range found in a normal control group (p=0.004). Conclusion ERT improved SSR continuously in Fabry patients in 2 years of observation. Although the mechanism of the SSR improvement is unknown, this response to ERT can be clinically significant if it reflects a normalization in sweating.

Abbreviations

CRI

chronic renal insufficiency

ESRD

end-stage renal disease

ERT

enzyme replacement therapy

FD

Fabry disease

Gb3

globotriaosyl ceramide

NE

neurological examination

PNS

peripheral nervous system

QSART

quantitative sudomotor axon reflex test

SSR

sympathetic skin response

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References

  1. Baser S (1991) Sudomotor function in autonomic failure. Neurology 41: 1564–1566.PubMedGoogle Scholar
  2. Beck M, Ricci R, Widmer U, et al (2004) Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 34: 838–844.PubMedCrossRefGoogle Scholar
  3. Brady RO, Schiffmann R (2000) Clinical features of and recent advances in therapy for Fabry disease. JAMA 284: 2771–2775.PubMedCrossRefGoogle Scholar
  4. Cable WJL, Kolodny EH, Adams RD (1982) Fabry's disease: impaired autonomic function. Neurology 32: 498–502.PubMedGoogle Scholar
  5. Desnick RJ, Ioannou YA, Eng CM (2001) alpha-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet al Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3733–3774.Google Scholar
  6. Dütsch M, Marthol H, Stemper B, Brys M, Haendl T, Hilz MJ (2002) Small fibre dysfunction predominates in Fabry neuropathy. J Clin Neurophysiol 19: 575–586.PubMedCrossRefGoogle Scholar
  7. Eng C, Denick R (1994) Molecular basis of Fabry disease: mutations and polymorphisms in the human alfa-galactosidase A gene. Hum Mut 3: 103–111.PubMedCrossRefGoogle Scholar
  8. Eng C, Guffon N, Wilcox WR, et al (2001) Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 345: 9–16.PubMedCrossRefGoogle Scholar
  9. Eto Y, Ohashi T, Utsunomiya Y, et al (2005) Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study. J Inherit Metab Dis 28(4): 575–583.PubMedCrossRefGoogle Scholar
  10. Gomes I, Nora D, Becker J, et al (2003) Nerve conduction studies, electromyography and sympathetic skin response in Fabry's disease. J Neurol Sci 214: 21–25.PubMedCrossRefGoogle Scholar
  11. Hahoff D, Enever Y, Quiney R, Zuckerman J, Macdermot K, Mehta (2003) Hearing loss in Fabry disease: the effect of agalsidase alfa replacement therapy. J Inherit Metab Dis 26: 787–794.CrossRefGoogle Scholar
  12. Hilz MJ, Stemper B, Kolodny EH (2000) Lower limb cold exposure induces pain and prolonged small fibre dysfunction in Fabry patients. Pain 84: 361–365.PubMedCrossRefGoogle Scholar
  13. Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M (2004) Enzyme replacement therapy improves function of C, Aδ-, and Aβ-nerve fibres in Fabry neuropathy. Neurology 62: 1066–1072.PubMedGoogle Scholar
  14. Jardim LB, Vedolin L, Schwartz IVD, et al (2004) CNS involvement in Fabry's disease: clinical and image studies before and after 12 months of enzyme replacement therapy. J Inherit Metab Dis 27(2): 229–240.PubMedCrossRefGoogle Scholar
  15. Kolodny EH, Pastores GM (2002) Anderson—Fabry disease: extrarenal, neurologic manifestations. J Am Soc Nephrol 13: S150–S153.PubMedGoogle Scholar
  16. Luciano CA, Russell JW, Banerjee T, et al (2002) Physiologic characterization of neuropathy in Fabry disease. Muscle Nerve 26: 622–629.PubMedCrossRefGoogle Scholar
  17. MacDermot KD, Holmes A, Miners AH (2001) Anderson—Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38: 750–760.PubMedCrossRefGoogle 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 Invest 34(March): 236–242.PubMedCrossRefGoogle Scholar
  19. Schiffmann R, Scott LJ (2000) Pathophysiology and assessment of neuropathic pain in Fabry disease. Acta Paediatr Suppl 91: 48–52.CrossRefGoogle Scholar
  20. Schiffman R, Kopp JB, Austin HA, et al (2001) Enzyme replacement therapy in Fabry disease. A randomised controlled trial. JAMA 285: 2743–2749.CrossRefGoogle Scholar
  21. Schiffmann R, Floeter MK, Dambrosia JM, et al (2003) Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 28: 703–710.PubMedCrossRefGoogle Scholar
  22. Shahani BT, Halperin JJ, Boulu P, Cohen J (1984) Sympathetic skin response: a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 47: 536–542.PubMedCrossRefGoogle Scholar
  23. Syed NA, Sandbrink, Luciano CA, et al (2000) Cutaneous silent periods in patients with Fabry disease. Muscle Nerve 23: 1179–1186.PubMedCrossRefGoogle Scholar
  24. Thurberg BL, Byers HR, Granter SR, Phelps RG, Gordon RE, O'Callaghan M (2004) Monitoring the 3 year efficacy of enzyme replacement therapy in Fabry disease by repeated skin biopsies. J Invest Dermatol 122: 900–908.PubMedCrossRefGoogle Scholar
  25. Weidemann F, Breunig F, Beer M, et al (2003) Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease. Circulation 108: 1299–1301.PubMedCrossRefGoogle Scholar
  26. Wilcox WR, Banikazemi M, Guffon N, et al (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75: 65–74.PubMedCrossRefGoogle Scholar
  27. Yamamoto K, Sobue G, Iwase S, Kumazawa K, Mitsuma T, Mano T (1996) Possible mechanism of anhidrosis in a symptomatic female carrier of Fabry's disease: an assessment by skin sympathetic nerve activity and sympathetic skin response. Clin Auton Res 6(2):107–110.PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  • L. B. Jardim
    • 1
    • 2
  • I. Gomes
    • 3
  • C. B. O. Netto
    • 1
  • D. B. Nora
    • 3
  • U. S. Matte
    • 4
  • F. Pereira
    • 1
    • 4
  • M. G. Burin
    • 1
  • L. Kalakun
    • 1
  • R. Giugliani
    • 1
    • 5
  • J. Becker
    • 3
  1. 1.Medical Genetics ServiceHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  2. 2.Internal Medicine DepartmentUniversidade Federal do Rio Grande do SulBrazil
  3. 3.Neurology ServiceHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  4. 4.Research CenterHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  5. 5.Biochemistry DepartmentUniversidade Federal do Rio Grande do SulBrazil

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