Skip to main content

Advertisement

SpringerLink
Log in

Significant improvement in Fabry disease podocytopathy after 3 years of treatment with agalsidase beta

  • Brief Report
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Fabry disease is an X-linked lysosomal disorder caused by decreased activity of α-galactosidase A (GLA). Consequent accumulation of globotriaosylceramide (GL-3) in lysosomes results in damage to a variety of organs, including the kidneys. Enzyme replacement therapy (ERT) is an effective treatment, but whether it should be started before organ damage is evident is a matter of debate.

Case diagnosis/treatment

A 10-year-old boy who complained of severe sole pain for 3 years had been misdiagnosed with juvenile idiopathic arthritis. Further investigations revealed decreased GLA activity and a M1T mutation in the GLA gene causing protein truncation, suggestive of Fabry disease. Despite normal renal function and urinalysis, renal biopsy showed abnormal structure, with marked accumulation of GL-3 in podocytes, partial effacement of foot processes and irregularly reduced expression of nephrin in the slit diaphragm. After 1 year of ERT with 1 mg/kg agalsidase beta once every 2 weeks, his pain had resolved with ERT combined with carbamazepine and pregabalin. After 3 years of the ERT, repeat biopsy showed little renal GL-3 deposition, resolution of foot process effacement, and a dramatic improvement in nephrin expression.

Conclusions

There may be a window of opportunity in which pain and renal injury can be addressed in the early stages of Fabry disease. Early initiation of ERT should therefore be considered for children with Fabry disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L (1967) Enzymatic defect in Fabry’s disease. Ceramidetrihexosidase deficiency. N Engl J Med 276:1163–1167

    Article  CAS  PubMed  Google Scholar 

  2. Marchesoni CL, Roa N, Pardal AM, Neumann P, Cáceres G, Martínez P, Kisinovsky I, Bianchi S, Tarabuso AL, Reisin RC (2010) Misdiagnosis in Fabry disease. J Pediatr 156:828–831

    Article  PubMed  Google Scholar 

  3. Burlina AP, Sims KB, Politei JM, Bennett GJ, Baron R, Sommer C, Møller AT, Hilz MJ (2011) Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel. BMC Neurol 11:61

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fogo AB, Bostad L, Svarstad E, Cook WJ, Moll S, Barbey F, Geldenhuys L, West M, Ferluga D, Vujkovac B, Howie AJ, Burns A, Reeve R, Waldek S, Noël LH, Grünfeld JP, Valbuena C, Oliveira JP, Müller J, Breunig F, Zhang X, Warnock DG; International Study Group of Fabry Nephropathy (ISGFN) (2010) Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN). Nephrol Dial Transplant 25:2168–2177

    Article  PubMed  Google Scholar 

  5. Machida H, Ito S, Hirose T, Takeshita F, Oshiro H, Nakamura T, Mori M, Inayama Y, Yan K, Kobayashi N, Yokota S (2010) Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis. Nephrol Dial Transplant 25:2530–2537

    Article  PubMed  Google Scholar 

  6. Choi L, Vernon J, Kopach O, Minett MS, Mills K, Clayton PT, Meert T, Wood JN (2015) The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain. Neurosci Lett 594:163–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lacomis D, Roeske-Anderson L, Mathie L (2005) Neuropathy and Fabry’s disease. Muscle Nerve 31:102–107

    Article  PubMed  Google Scholar 

  8. Pagnini I, Borsini W, Cecchi F, Sgalambro A, Olivotto I, Frullini A, Cimaz R (2011) Distal extremity pain as a presenting feature of Fabry’s disease. Arthritis Care Res (Hoboken) 63:390–395

    Google Scholar 

  9. Kanai T, Yamagata T, Ito T, Odaka J, Saito T, Aoyagi J, Kobayashi M, Ohashi T, Ueda Y, Momoi MY (2011) Foot process effacement with normal urinalysis in classic Fabry disease. JIMD Rep 1:39–42

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tøndel C, Bostad L, Larsen KK, Hirth A, Vikse BE, Houge G, Svarstad E (2013) Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol 24:137–148

    Article  PubMed  Google Scholar 

  11. Tøndel C, Kanai T, Larsen KK, Ito S, Politei JM, Warnock DG, Svarstad E (2015) Foot process effacement is an early marker of nephropathy in young classic Fabry patients without albuminuria. Nephron 129:16–21

    Article  PubMed  Google Scholar 

  12. Grahammer F, Schell C, Huber TB (2013) The podocyte slit diaphragm—from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9:587–598

    Article  CAS  PubMed  Google Scholar 

  13. Germain DP, Waldek S, Banikazemi M, Bushinsky DA, Charrow J, Desnick RJ, Lee P, Loew T, Vedder AC, Abichandani R, Wilcox WR, Guffon N (2007) Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 18:1547–1557

    Article  CAS  PubMed  Google Scholar 

  14. Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ, Fabry Disease Clinical Trial Study Group (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146:77–86

    Article  PubMed  Google Scholar 

  15. Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, Lemay R, Linthorst GE, Packman S, Scott CR, Waldek S, Warnock DG, Weinreb NJ, Wilcox WR (2015) Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet 52:353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Warnock DG, Ortiz A, Mauer M, Linthorst GE, Oliveira JP, Serra AL, Maródi L, Mignani R, Vujkovac B, Beitner-Johnson D, Lemay R, Cole JA, Svarstad E, Waldek S, Germain DP, Wanner C, Registry F (2012) Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation. Nephrol Dial Transplant 27:1042–1049

    Article  CAS  PubMed  Google Scholar 

  18. Cimaz R, Guillaume S, Hilz MJ, Horneff G, Manger B, Thorne JC, Møller AT, Wulffraat NM, Roth J (2011) Awareness of Fabry disease among rheumatologists—current status and perspectives. Clin Rheumatol 30:467–475

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

We wish to thank Dr Kimitoshi Nakamura (Kumamoto University) for undertaking the enzyme activity test and genetic analysis.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Shuichi Ito

  2. Division of Pediatric Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

    Shuichi Ito, Masao Ogura & Koichi Kamei

  3. Division of Pathology, National Center for Child Health and Development, Tokyo, Japan

    Kentaro Matsuoka

  4. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    David G. Warnock

Authors
  1. Shuichi Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masao Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Koichi Kamei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kentaro Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David G. Warnock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuichi Ito.

Ethics declarations

Conflicts of interest

None of the authors has any conflicts of interest to declare.

Ethics approval

All procedures performed in studies involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments, or comparable ethical standards.

Informed consent

Informed consent for publication of this case was obtained from the child and his parents.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ito, S., Ogura, M., Kamei, K. et al. Significant improvement in Fabry disease podocytopathy after 3 years of treatment with agalsidase beta. Pediatr Nephrol 31, 1369–1373 (2016). https://doi.org/10.1007/s00467-016-3387-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-016-3387-4

Keywords

Search

Navigation