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CEN Case Reports

, Volume 6, Issue 2, pp 210–214 | Cite as

Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical and pathological evaluations by repeat kidney biopsy and a successful pregnancy

  • Yoichi IwafuchiEmail author
  • Hiroki Maruyama
  • Tetsuo Morioka
  • Seiko Noda
  • Hiroshi Nagata
  • Yuko Oyama
  • Ichiei Narita
Case Report

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipid catabolism caused by deficient activity of the lysosomal hydrolase alpha-galactosidase A (ɑ-Gal A). A 20-year-old woman was referred to our hospital because of proteinuria and persistent macroscopic hematuria. Based on the typical renal pathological findings, deficient activity of the ɑ-Gal A, and heterozygous mutation in the ɑ-Gal A gene, she was diagnosed with Fabry disease. After 1 year of enzyme replacement therapy with agalsidase alfa at 0.2 mg/kg every other week, the patient’s proteinuria and hematuria were disappeared. In our patient, enzyme replacement therapy with agalsidase alfa was observed to be safe and well-tolerated during her pregnancy, with no significant negative effects on her or her child. Here, we report clinical and pathological evaluations of a patient through repeat kidney biopsy after 6 years of enzyme replacement therapy. Furthermore, we discussed the appropriate enzyme replacement therapy and its safety in pregnant women with Fabry disease.

Keywords

Heterozygous Fabry disease Enzyme replacement therapy Agalsidase alfa Agalsidase beta Kidney biopsy Pregnancy 

Notes

Acknowledgements

The authors are grateful to Mr. N. Sakamoto, Ms. S. Tsuchida, Ms. M. Yoshinuma, and Ms. M. Igashima (Department of Pathology, Shinrakuen Hospital) for their technical assistance.

Compliance with ethical standards

Conflict of interest

H. M. has received speaker fees, research support from Sanofi. I. N. has received donations for research from Sanofi and Sumitomo Dainippon Pharm.

Human and animal rights statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Desnick RJ, Ioannou YA, Eng CM. Alpha-galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited diseases, 8th edn. New York: McGraw-Hill; 2001. pp. 3733–74.Google Scholar
  2. 2.
    Biegstraaten M, Arngrímsson R, Barbey F, Boks L, Cecchi F, Deegan PB, Feldt-Rasmussen U, Geberhiwot T, Germain DP, Hendriksz C, Hughes DA, Kantola I, Karabul N, Lavery C, Linthorst GE, Mehta A, van de Mheen E, Oliveira JP, Parini R, Ramaswami U, Rudnicki M, Serra A, Sommer C, Sunder-Plassmann G, Svarstad E, Sweeb A, Terryn W, Tylki-Szymanska A, Tøndel C, Vujkovac B, Weidemann F, Wijburg FA, Woolfson P, Hollak CE. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Orphanet J Rare Dis. 2015;10:36.CrossRefGoogle Scholar
  3. 3.
    Schiffmann R, Hughes DA, Linthorst GE, Ortiz A, Svarstad E, Warnock DG, West ML, Wanner C. Conference participants. screening, diagnosis, and management of patients with Fabry disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2017;91:284–93.CrossRefGoogle Scholar
  4. 4.
    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, Fabry Registry. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation. Nephrol Dial Transpl. 2012;27:1042–9.CrossRefGoogle Scholar
  5. 5.
    Thurberg BL, Rennke H, Colvin RB, Dikman S, Gordon RE, Collins AB, Desnick RJ, O’Callaghan M. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int. 2002;62:1933–46.CrossRefGoogle Scholar
  6. 6.
    Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001;285:2743–9.CrossRefGoogle Scholar
  7. 7.
    Tøndel C, Bostad L, Larsen KK, Hirth A, Vikse BE, Houge G, Svarstad E. Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol. 2013;24:137 – 48.CrossRefGoogle Scholar
  8. 8.
    Lukas J, Scalia S, Eichler S, Pockrandt AM, Dehn N, Cozma C, Giese AK, Rolfs A. Functional and clinical consequences of novel α-galactosidase A mutations in Fabry disease. Hum Mutat. 2016;37:43–51.CrossRefGoogle Scholar
  9. 9.
    Nowak A, Mechtler T, Kasper DC, Desnick RJ. Correlation of Lyso-Gb3 levels in dried blood spots and sera from patients with classic and Later-Onset Fabry disease. Mol Genet Metab. 2017;121:320–4.CrossRefGoogle Scholar
  10. 10.
    Tøndel C, Kanai T, Larsen KK, Ito S, Politei JM, Warnock DG. Foot process effacement is an early marker of nephropathy in young classic Fabry patients without albuminuria. Nephron. 2015;129:16–21.CrossRefGoogle Scholar
  11. 11.
    Hoffmann B. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring. Orphanet J Rare Dis. 2009;4:21.CrossRefGoogle Scholar
  12. 12.
    Ito S, Ogura M, Kamei K, Matsuoka K, Warnock DG. Significant improvement in Fabry disease podocytopathy after 3 years of treatment with agalsidase beta. Pediatr Nephrol. 2016;31:1369–73.CrossRefGoogle Scholar
  13. 13.
    Wendt S, Whybra C, Kampmann C, Teichmann E, Beck M. Successful pregnancy outcome in a patient with Fabry disease receiving enzyme replacement therapy with agalsidase alfa. J Inherit Metab Dis. 2005;28:787–8.CrossRefGoogle Scholar
  14. 14.
    Senocak Tasci E, Bicik Z. Safe and successful treatment with agalsidase beta during pregnancy in Fabry disease. Iran J Kidney Dis. 2015;9:406–8.PubMedGoogle Scholar
  15. 15.
    Brady RO, Uhlendorf BW, Jacobson CB. Fabry’s disease: antenatal detection. Science. 1971;172:174–5.CrossRefGoogle Scholar
  16. 16.
    Vedder AC, Strijland A, vd Bergh Weerman MA, Florquin S, Aerts JM, Hollak CE. Manifestations of Fabry disease in placental tissue. J Inherit Metab Dis. 2006;29:106 – 11.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2017

Authors and Affiliations

  1. 1.Department of Internal MedicineKoseiren Sanjo General HospitalSanjoJapan
  2. 2.Department of Clinical NephroscienceNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  3. 3.Department of Internal Medicine, Kidney CenterShinrakuen HospitalNiigataJapan
  4. 4.Department of Obstetrics and GynecologyKoseiren Sanjo General HospitalSanjoJapan
  5. 5.Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

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