Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical and pathological evaluations by repeat kidney biopsy and a successful pregnancy
- 219 Downloads
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.
KeywordsHeterozygous Fabry disease Enzyme replacement therapy Agalsidase alfa Agalsidase beta Kidney biopsy Pregnancy
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 was obtained from all individual participants included in the study.
- 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.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.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.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