Display options
Cite
Terryn W, Vanholder R, Hemelsoet D, et al. Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT. JIMD Rep. 2012;8:101-8doi: 10.1007/8904_2012_167.
Terryn, W., Vanholder, R., Hemelsoet, D., Leroy, B. P., Van Biesen, W., De Schoenmakere, G., Wuyts, B., Claes, K., De Backer, J., De Paepe, G., Fogo, A., Praet, M., & Poppe, B. (2013). Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT. JIMD reports, 8101-8. https://doi.org/10.1007/8904_2012_167
Terryn, W, et al. "Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT." JIMD reports vol. 8 (2013): 101-8. doi: https://doi.org/10.1007/8904_2012_167
Terryn W, Vanholder R, Hemelsoet D, Leroy BP, Van Biesen W, De Schoenmakere G, Wuyts B, Claes K, De Backer J, De Paepe G, Fogo A, Praet M, Poppe B. Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT. JIMD Rep. 2013;8:101-8. doi: 10.1007/8904_2012_167. Epub 2012 Jul 29. PMID: 23430526; PMCID: PMC3565658.
Copy Download .nbib Format: NLM
Share it on

JIMD Rep. 2013;8:101-8. doi: 10.1007/8904_2012_167. Epub 2012 Jul 29.

Questioning the Pathogenic Role of the GLA p.Ala143Thr "Mutation" in Fabry Disease: Implications for Screening Studies and ERT.

JIMD reports

W Terryn, R Vanholder, D Hemelsoet, B P Leroy, W Van Biesen, G De Schoenmakere, B Wuyts, K Claes, J De Backer, G De Paepe, A Fogo, M Praet, B Poppe

Affiliations

  1. Department of Internal Medicine, Division of Nephrology, Regional Hospital Jan Yperman, Ypres, Briekestraat 12, Ieper, 8900, Belgium, [email protected].

PMID: 23430526 PMCID: PMC3565658 DOI: 10.1007/8904_2012_167

Abstract

Fabry disease is an X-linked inborn error of glycosphingolipid metabolism caused by quantitative or qualitative defects in the lysosomal enzyme alfa-Galactosidase A (aGAL A), ultimately resulting in vital organ dysfunction. Mainly the kidneys, the heart, and the central nervous system are involved. While the classical phenotype of Fabry disease is readily recognizable, screening studies have identified clinical variants. Here, we report the phenotype associated with the GLA p.Ala143Thr (c.427G>A) mutation in 12 patients aged 42-83 years. None of the patients had classical Fabry signs or symptoms as angiokeratoma, hypohidrosis, acroparesthesia, or cornea verticillata. Possible Fabry manifestations were renal failure (5/12), stroke (7/12), and left ventricular hypertrophy (5/12), but these were not necessarily attributable to the p.Ala143Thr mutation, as a cardiac biopsy in one female and left ventricular hypertrophy and kidney biopsies in two males with renal failure and microalbuminuria lacked Gb-3 deposits. The literature data on this mutation as well as data collected in the Fabry Outcome Survey (FOS) database confirm these findings. The association of renal failure, stroke, and left ventricular hypertrophy with this mutation could be the result of selection bias, as most patients were detected in screening studies.We conclude that care should be taken with attribution of vital organ dysfunction to GLA sequence alterations. In case of the p.Ala143Thr mutation, and possibly also other mutations associated with an attenuated phenotype, diagnostic tools such as biopsy and imaging should critically evaluate the relation of end-organ failure with Fabry disease, as this has important consequences for enzyme replacement therapy.

References

  1. J Am Coll Cardiol. 2007 Dec 18;50(25):2399-403 - PubMed
  2. Nephrol Dial Transplant. 2008 Jan;23(1):294-300 - PubMed
  3. Genet Med. 2006 Sep;8(9):539-48 - PubMed
  4. Am J Hum Genet. 2006 Jul;79(1):31-40 - PubMed
  5. PLoS One. 2012;7(4):e36373 - PubMed
  6. N Engl J Med. 1995 Aug 3;333(5):288-93 - PubMed
  7. Lancet. 2012 Jan 28;379(9813):335-41 - PubMed
  8. Clin Chim Acta. 2001 Jun;308(1-2):195-6 - PubMed
  9. Mol Med. 1997 Mar;3(3):174-82 - PubMed
  10. Nephrol Ther. 2012 Nov;8(6):433-8 - PubMed
  11. Science. 1970 Feb 27;167(3922):1268-9 - PubMed
  12. Eur J Hum Genet. 2011 Nov;19(11):1111 - PubMed
  13. J Am Soc Nephrol. 2002 Jun;13 Suppl 2:S139-43 - PubMed
  14. Circ Cardiovasc Genet. 2009 Oct;2(5):450-6 - PubMed
  15. Nephrol Dial Transplant. 2008 Dec;23(12):4044-8 - PubMed
  16. N Engl J Med. 1967 May 25;276(21):1163-7 - PubMed
  17. N Engl J Med. 1991 Feb 7;324(6):395-9 - PubMed
  18. Stroke. 2010 May;41(5):863-8 - PubMed
  19. Heart. 2011 Dec;97(23):1957-60 - PubMed
  20. Chem Phys Lipids. 2011 Sep;164(6):590-606 - PubMed

Publication Types