Skip to main content

A case of female Fabry disease revealed by renal biopsy


Fabry disease (FD) is an X-linked inherited glycosphingolipid metabolism disorder, therefore, heterozygous female FD patients display highly variable clinical symptoms, disease severity, and pathological findings. This makes it very challenging to diagnosing female patients with FD. A 69-year-old Japanese female was introduced to the nephrologist for the evaluation of proteinuria. A renal biopsy was performed. Although the light microscopic examinations revealed that most of the glomeruli showed minor glomerular abnormalities, however, vacuolation was apparently found in the tubular epithelial cells. Immunofluorescence staining for globotriaosylceramide was positively detected in some podocytes and distal tubular epithelial cells. In addition, myelin-like structure (zebra body) was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, biochemical and genetic analysis confirmed the diagnosis of female FD. Enzyme replacement therapy was performed in conjunction with renin–angiotensin aldosterone system inhibitors and beta-blockers. The patient’s family members received the analysis, and the same DNA missense mutation was detected in the patient’s grandson. The enzyme replacement therapy was introduced to the grandson. The present case showed that renal biopsy can contribute towards a correct diagnosis for FD. Particularly, in female FD patients, careful examination of pathological changes is essential, for example, vacuolation of any type of renal cells may be a clue for the diagnosis.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry's disease: ceramidetrihexosidase deficiency. N Engl J Med. 1967;27:163–7.

    Google Scholar 

  2. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.

    Article  Google Scholar 

  3. Garman SC, Garboczi DN. The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol. 2004;337:319–35.

    CAS  Article  Google Scholar 

  4. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008;93:112–28.

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

  6. Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, Yeh HY, Chao MC, Lin SJ, Kitagawa T, Desnick RJ, Hsu LW. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G%3eA (IVS4+919G%3eA). Hum Mutat. 2009;30:1397–405.

  7. Linthorst GE, Bouwman MG, Wijburg FA, Aerts JM, Poorthuis BJ, Hollak CE. Screening for Fabry disease in high-risk populations: a systematic review. J Med Genet. 2010;47:217–22.

    CAS  Article  Google Scholar 

  8. Takahashi N, Yokoi S, Kasuno K, Kogami A, Tsukimura T, Togawa T, Saito S, Ohno K, Hara M, Kurosawa H, Hirayama Y, Kurose T, Yokoyama Y, Mikami D, Kimura H, Naiki H, Sakuraba H, Iwano M. A heterozygous female with Fabry disease due to a novel alpha-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes. Clin Nephrol. 2015;83:301–8.

    CAS  Article  Google Scholar 

  9. Najafian B, Fogo AB, Lusco MA, Alpers CE. AJKD atlas of renal pathology: Fabry nephropathy. Am J Kidney Dis. 2015;66:e35–e3636.

    Article  Google Scholar 

  10. Alroy J, Sabnis S, Kopp JB. Renal pathology in Fabry disease. J Am Soc Nephrol. 2002;13(Suppl 2):S134–S138138.

    Article  Google Scholar 

  11. Najafian B, Svarstad E, Bostad L, Gubler MC, Tondel C, Whitley C, Mauer M. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011;79:663–70.

    CAS  Article  Google Scholar 

  12. Fischer EG, Moore MJ, Lager DJ. Fabry disease: a morphologic study of 11 cases. Mod Pathol. 2006;19:1295–301.

    Article  Google Scholar 

  13. Gubler MC, Lenoir G, Grunfeld JP, Ulmann A, Droz D, Habib R. Early renal changes in hemizygous and heterozygous patients with Fabry's disease. Kidney Int. 1978;13:223–35.

    CAS  Article  Google Scholar 

  14. 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, Noel LH, Grunfeld JP, Valbuena C, Oliveira JP, Muller J, Breunig F, Zhang X, Warnock DG. Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN). Nephrol Dial Transpl. 2010;25:2168–77.

    Article  Google Scholar 

  15. Ortiz A, Oliveira JP, Waldek S, Warnock DG, Cianciaruso B, Wanner C. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transpl. 2008;23:1600–7.

    CAS  Article  Google Scholar 

  16. Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, Maseri A, Frustaci A. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation. 2004;110:1047–53.

    CAS  Article  Google Scholar 

  17. Kobayashi M, Ohashi T, Sakuma M, Ida H, Eto Y. Clinical manifestations and natural history of Japanese heterozygous females with Fabry disease. J Inherit Metab Dis. 2008;31(Suppl 3):483–7.

    Article  Google Scholar 

  18. Schiffmann R, Warnock DG, Banikazemi M, Bultas J, Linthorst GE, Packman S, Sorensen SA, Wilcox WR, Desnick RJ. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transpl. 2009;24:2102–11.

    Article  Google Scholar 

  19. Warnock DG, Thomas CP, Vujkovac B, Campbell RC, Charrow J, Laney DA, Jackson LL, Wilcox WR, Wanner C. Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy. J Med Genet. 2015;52:860–6.

    CAS  Article  Google Scholar 

Download references


We are grateful to Honorary Prof. Nobuaki Yamanaka, Mr. Takashi Arai, Ms. Ms. Mitsue Kataoka, Ms. Kyoko Wakamatsu, Ms. Arimi Ishikawa, and Ms. Naomi Kuwahara for their expert assistance.


The authors have no funding sources to declare.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Sae Aratani.

Ethics declarations

Conflict of interest

The authors have no competing interests to declare.

Ethical approval

All the procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This case study complied with the Helsinki Declaration standards and was approved by the Ethical Committee of Nippon Medical School Hospital.

Informed consent

Informed consent was obtained from the patient included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Aratani, S., Yamakawa, H., Suzuki, S. et al. A case of female Fabry disease revealed by renal biopsy. CEN Case Rep 9, 24–29 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Fabry disease
  • Renal biopsy
  • Pathology
  • Vacuolation
  • Enzyme replacement therapy