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Fabry Disease

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Pediatric Nephrology

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Abstract

Fabry disease is a rare lysosomal storage disorder, caused by the deficiency of the enzyme alpha-galactosidase A that is responsible for the degradation of the sphingolipid globotriaosylceramide, also called Gb3. Due to the insufficient activity of alpha-galactosidase A, Gb3 accumulates in a variety of cells of the body, resulting in progressive organ damage. Fabry disease is an X-linked disorder in which also females are affected, although often less severely than males. Clinically, this multisystemic disorder is characterized by neuropathic pain, gastrointestinal disturbances, typical skin lesions, sweating difficulties, and kidney and heart failure. Life expectancy is significantly reduced, whereby in both males and females, renal and cardiac diseases are the primary causes of death. In children, pain in hands and feet (acroparesthesia) and abdominal cramps are the leading symptoms; further clinical manifestations include corneal opacities, called cornea verticillata, and skin abnormalities (angiokeratoma). Albuminuria and an increased heart size represent the first signs of renal and cardiac manifestation that can be present already in young patients. Besides symptomatic and supplementary treatment such as analgesics, drugs for kidney dysfunction and for blood pressure control, enzyme replacement therapy is available for children with Fabry disease.

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References

  1. Sandhoff K. Metabolic and cellular bases of sphingolipidoses. Biochem Soc Trans. 2013;41(6):1562–8. https://doi.org/10.1042/BST20130083.

    Article  CAS  PubMed  Google Scholar 

  2. Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 2008;105(8):2812–7. https://doi.org/10.1073/pnas.0712309105.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Varela P, Caldas MM, Pesquero JB. Novel GLA mutation promotes intron inclusion leading to Fabry disease. Front Genet. 2019;10:783. https://doi.org/10.3389/fgene.2019.00783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagege AA, Eladari D, Jabbour F, Beldjord C, De Mazancourt P, Germain DP. X-chromosome inactivation in female patients with Fabry disease. Clin Genet. 2016;89(1):44–54. https://doi.org/10.1111/cge.12613.

    Article  CAS  PubMed  Google Scholar 

  5. Beck M, Cox TM. Comment: why are females with Fabry disease affected? Mol Genet Metab Rep. 2019;21:100529. https://doi.org/10.1016/j.ymgmr.2019.100529.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Investig. 2004;34(3):236–42.

    Article  CAS  Google Scholar 

  7. Inoue T, Hattori K, Ihara K, Ishii A, Nakamura K, Hirose S. Newborn screening for Fabry disease in Japan: prevalence and genotypes of Fabry disease in a pilot study. J Hum Genet. 2013;58(8):548–52. https://doi.org/10.1038/jhg.2013.48.

    Article  CAS  PubMed  Google Scholar 

  8. Hsu TR, Hung SC, Chang FP, Yu WC, Sung SH, Hsu CL, Dzhagalov I, Yang CF, Chu TH, Lee HJ, Lu YH, Chang SK, Liao HC, Lin HY, Liao TC, Lee PC, Li HY, Yang AH, Ho HC, Chiang CC, Lin CY, Desnick RJ, Niu DM. Later onset Fabry disease, cardiac damage progress in silence: experience with a highly prevalent mutation. J Am Coll Cardiol. 2016;68(23):2554–63. https://doi.org/10.1016/j.jacc.2016.09.943.

    Article  PubMed  Google Scholar 

  9. Hilz MJ, Stemper B, Kolodny EH. Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain. 2000;84(2–3):361–5. https://doi.org/10.1016/s0304-3959(99)00236-5.

    Article  CAS  PubMed  Google Scholar 

  10. Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, Widmer U, Beck M, Investigators FOSE. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr. 2006;95(1):86–92. https://doi.org/10.1080/08035250500275022.

    Article  PubMed  Google Scholar 

  11. Kalkum G, Pitz S, Karabul N, Beck M, Pintos-Morell G, Parini R, Rohrbach M, Bizjajeva S, Ramaswami U. Paediatric Fabry disease: prognostic significance of ocular changes for disease severity. BMC Ophthalmol. 2016;16(1):202. https://doi.org/10.1186/s12886-016-0374-2.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Schachern PA, Shea DA, Paparella MM, Yoon TH. Otologic histopathology of Fabry’s disease. Ann Otol Rhinol Laryngol. 1989;98(5 Pt 1):359–63. https://doi.org/10.1177/000348948909800509.

    Article  CAS  PubMed  Google Scholar 

  13. Suntjens E, Dreschler WA, Hess-Erga J, Skrunes R, Wijburg FA, Linthorst GE, Tondel C, Biegstraaten M. Hearing loss in children with Fabry disease. J Inherit Metab Dis. 2017;40(5):725–31. https://doi.org/10.1007/s10545-017-0051-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Branton MH, Schiffmann R, Sabnis SG, Murray GJ, Quirk JM, Altarescu G, Goldfarb L, Brady RO, Balow JE, Austin Iii HA, Kopp JB. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore). 2002;81(2):122–38.

    Article  CAS  Google Scholar 

  15. Wijburg FA, Benichou B, Bichet DG, Clarke LA, Dostalova G, Fainboim A, Fellgiebel A, Forcelini C, An Haack K, Hopkin RJ, Mauer M, Najafian B, Scott CR, Shankar SP, Thurberg BL, Tondel C, Tylki-Szymanska A, Ramaswami U. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial. PLoS One. 2015;10(5):e0124987. https://doi.org/10.1371/journal.pone.0124987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Elleder M, Poupetova H, Kozich V. [Fetal pathology in Fabry’s disease and mucopolysaccharidosis type I]. Cesk Patol. 1998;34(1):7–12.

    Google Scholar 

  17. Kampmann C, Wiethoff CM, Whybra C, Baehner FA, Mengel E, Beck M. Cardiac manifestations of Anderson-Fabry disease in children and adolescents. Acta Paediatr. 2008;97(4):463–9.

    Article  Google Scholar 

  18. Bugescu N, Alioto A, Segal S, Cordova M, Packman W. The neurocognitive impact of Fabry disease on pediatric patients. Am J Med Genet B Neuropsychiatr Genet. 2015;168B(3):204–10. https://doi.org/10.1002/ajmg.b.32297.

    Article  PubMed  Google Scholar 

  19. Cuestas D, Perafan A, Forero Y, Bonilla J, Velandia A, Gutierrez A, Motta A, Herrera H, Rolon M. Angiokeratomas, not everything is Fabry disease. Int J Dermatol. 2019;58(6):713–21. https://doi.org/10.1111/ijd.14330.

    Article  PubMed  Google Scholar 

  20. Nowak A, Mechtler TP, Desnick RJ, Kasper DC. Plasma LysoGb3: a useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes. Mol Genet Metab. 2017;120(1–2):57–61. https://doi.org/10.1016/j.ymgme.2016.10.006.

    Article  CAS  PubMed  Google Scholar 

  21. Burlina AP, Sims KB, Politei JM, Bennett GJ, Baron R, Sommer C, Moller AT, Hilz MJ. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel. BMC Neurol. 2011;11:61. https://doi.org/10.1186/1471-2377-11-61.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ramaswami U, Parini R, Pintos-Morell G, Kalkum G, Kampmann C, Beck M, Investigators FOS. Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey. Clin Genet. 2012;81(5):485–90. https://doi.org/10.1111/j.1399-0004.2011.01671.x.

    Article  CAS  PubMed  Google Scholar 

  23. Mohrenschlager M, Braun-Falco M, Ring J, Abeck D. Fabry disease: recognition and management of cutaneous manifestations. Am J Clin Dermatol. 2003;4(3):189–96. https://doi.org/10.2165/00128071-200304030-00005.

    Article  PubMed  Google Scholar 

  24. Tondel C, Ramaswami U, Aakre KM, Wijburg F, Bouwman M, Svarstad E. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate. Nephrol Dial Transplant. 2010;25(5):1507–13. https://doi.org/10.1093/ndt/gfp658.

    Article  PubMed  Google Scholar 

  25. Ren H, Li L, Yu J, Wu S, Zhou S, Zheng Y, Sun W. Fabry disease and immunoglobulin A nephropathy presenting with Alport syndrome-like findings: a case report. Medicine (Baltimore). 2019;98(28):e16256. https://doi.org/10.1097/md.0000000000016256.

    Article  Google Scholar 

  26. Wu H, Behera TR, Gong J, Shen Q. Coexistence of Fabry disease with IgM nephropathy: a case report. Medicine (Baltimore). 2019;98(41):e17566. https://doi.org/10.1097/md.0000000000017566.

    Article  Google Scholar 

  27. Arends M, Biegstraaten M, Wanner C, Sirrs S, Mehta A, Elliott PM, Oder D, Watkinson OT, Bichet DG, Khan A, Iwanochko M, Vaz FM, van Kuilenburg ABP, West ML, Hughes DA, Hollak CEM. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study. J Med Genet. 2018;55(5):351–8. https://doi.org/10.1136/jmedgenet-2017-104863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Spada M, Baron R, Elliott PM, Falissard B, Hilz MJ, Monserrat L, Tondel C, Tylki-Szymanska A, Wanner C, Germain DP. The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease – a systematic literature review by a European panel of experts. Mol Genet Metab. 2019;126(3):212–23. https://doi.org/10.1016/j.ymgme.2018.04.007.

    Article  CAS  PubMed  Google Scholar 

  29. Tondel 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(1):137–48. https://doi.org/10.1681/ASN.2012030316.

    Article  CAS  PubMed  Google Scholar 

  30. Lenders M, Nordbeck P, Kurschat C, Karabul N, Kaufeld J, Hennermann JB, Patten M, Cybulla M, Muntze J, Uceyler N, Liu D, Das AM, Sommer C, Pogoda C, Reiermann S, Duning T, Gaedeke J, Stumpfe K, Blaschke D, Brand SM, Mann WA, Kampmann C, Muschol N, Canaan-Kuhl S, Brand E. Treatment of Fabry’s disease with migalastat: outcome from a prospective observational multicenter study (FAMOUS). Clin Pharmacol Ther. 2020;108:326–37. https://doi.org/10.1002/cpt.1832.

    Article  CAS  PubMed  Google Scholar 

  31. Kriegsmann J, Otto M, Wandel E, Schwarting A, Faust J, Hansen T, Beck J, Whybra C, Beck M. [Fabry’s disease, glomerulonephritis with crescentic and granulomatous interstitial nephritis. Case of one family]. Pathologe. 2003;24(6):439–43. https://doi.org/10.1007/s00292-003-0659-0.

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Authors and Affiliations

  1. Institute of Clinical Science, SphinCS GmbH, Hochheim, Germany

    Michael Beck

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  1. Michael Beck
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Correspondence to Michael Beck .

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Editors and Affiliations

  1. Division of Nephrology, Bambino Gesù Children’s Hospital –, ROMA, Roma, Italy

    Francesco Emma

  2. Division of Nephrology and Hypertension The Heart Institute, University of Cincinnati Cincinnati Children’s Hospital Medical C, Cincinnati, OH, USA

    Stuart Goldstein

  3. Division of Nephrology, All India Institute of Medical Sciences, Ansari Nagar East, Delhi, India

    Arvind Bagga

  4. Division of Pediatric Nephrology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Carlton M. Bates

  5. Renal Unit, Graet Ormond Street Hospital, London, UK

    Rukshana Shroff

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Beck, M. (2021). Fabry Disease. In: Emma, F., Goldstein, S., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_106-1

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  • DOI: https://doi.org/10.1007/978-3-642-27843-3_106-1

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-27843-3

  • Online ISBN: 978-3-642-27843-3

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