Pediatric presentation of Fabry disease: common symptoms leading to the diagnosis of a rare disease
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Abstract
Fabry disease (FD) is a disease of genetic origin linked to the x chromosome. It occurs due to an inborn error in the metabolism of glycosphigolipids (GSL), mainly lobotriasylceramide (Gb3), secondary to deficiency of the enzyme alpha-galactosidase A (alfa-Gal). The alfa-Gal enzyme deficiency causes progressive accumulation of Gb3 within the lysosome, leading to
complications in different organs and body systems. This storage explains the occurrence of the first symptoms during childhood, characterized by pain, sensitivity to heat and cold, gastrointestinal disease, emphasizing recurrent abdominal pain and diarrhea. Here we report a case of FD in a male child and emphasize the importance of the clinical signs and
symptoms that the pediatrician gives to the diagnosis of the disease during early childhood.
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References
1. Cordeiro CA, Oréfice F, Lasmar EP, Santos HH, Valadares ER. Córnea verticilata - marcador clínico da doença de Fabry: relato de caso. Arq Bras Oftalmol. 2007;70(4):701-5. https://doi.org/10.1590/S0004-27492007000400024.
2. Biagini G, Almeida ACSF, Almeida TVR, Silva CAB, Castro BF de, Reche TC, et al. Case report: is low α-Gal enzyme activity suffcient to establish the diagnosis of Fabry disease? J Bras Nefrol. 2017;39(3):333-336. DOI: 10.5935/0101-2800.20170057.
3. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. DOI: 10.1186/1750-1172-5-30.
4. Blom D, Speijer D, Linthorst GE, Donker-Koopman WG, Strijland A, Aerts JMFG. Recombinant Enzyme Therapy for Fabry Disease: Absence of Editing of Human α-Galactosidase A mRNA. Am J Hum Genet. 2003;72(1):23-31. DOI: 10.1086/345309.
5. Elstein D, Schachamorov E, Beeri R, Altarescu G. X-inactivation in Fabry disease. Gene. 2012;505(2):266-8. DOI: 10.1016/j.gene.2012.06.013. Epub 2012 Jun 16.
6. Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, et al. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016;375(6):545-55. DOI: 10.1056/NEJMoa1510198.
7. Laney DA, Peck DS, Atherton AM, Manwaring LP, Christensen KM, Shankar SP, et al. Fabry disease in infancy and early childhood: a systematic literature review. Genet Med Off J Am Coll Med Genet. 2015;17(5):323-30.
8. Wang RY, Bodamer OA, Watson MS, Wilcox WR; ACMG Work Group on Diagnostic Confirmation of Lysosomal Storage Diseases. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet Med. 2011;13(5):457-84. DOI: 10.1097/GIM.0b013e318211a7e1.
9. Rozenfeld PA. Fabry disease: treatment and diagnosis. IUBMB Life. 2009;61(11):1043-1050. DOI:10.1002/iub.257.
10. Prabakaran T, Birn H, Bibby BM, Regeniter A, Sørensen SS, Feldt-Rasmussen U, Nielsen R, Christensen EI. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease. Nephrol Dial Transplant. 2014 Mar;29(3):619-25. DOI: 10.1093/ndt/gft452.
11. Hopkin RJ, Bissler J, Banikazemi M, Clarke L, Eng CM, Germain DP, Lemay R, Tylki-Szymanska A, Wilcox WR. Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry. Pediatr Res. 2008;64(5):550-5. DOI: 10.1203/PDR.0b013e318183f132.
12. Ries M, Gupta S, Moore DF, Sachdev V, Quirk JM, Murray GJ, et al. Pediatric Fabry Disease. Pediatrics. 2005;115(3):e344-e355. DOI: https://doi.org/10.1542/peds.2004-1678
13. Ries, M, Ramaswami, U, Parini, R, et al. The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents. Eur J Pediatr. 2003;162:767-772. https://doi.org/10.1007/s00431-003-1299-3
14. Hilz MJ, Stemper B, Kolodny EH. Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Department of Neurology, New York University, New York, NY, USA. Pain. 2000;84(2-3):361-365 Doi: 10.1016/s0304-3959(99)00236-5
15. Hoffmann B, Reinhardt D, Koletzko B. Effect of enzyme-replacement therapy on gastrointestinal symptoms in Fabry disease. Eur J Gastroenterol Hepatol. 2004;16(10):1067-9. DOI: 10.1097/00042737-200410000-00020
16. Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr. 2004;144(5 Suppl):S20-6. DOI: 10.1016/j.jpeds.2004.01.051
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;97:463-469
18. Havranek S, Linhart A, Urbanova Z, Ramaswam U. Early cardiac changes in children with Anderson-Fabry. JIMD Rep. 2013;11:53-64. DOI: 10.1007/8904_2013_222
19. Mehta A, Beck M, Sunder-Plassmann G, Ramaswami U, Parini R, Pintos-Morell G. Natural history and effects of enzyme replacement therapy in children and adolescents with Fabry disease. Oxford PharmaGenesis; 2006. Chapter 31.
20. Najafian B, Svarstad E, Bostad L, Gubler M-C, Tøndel C, Whitley C, et al. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011;79(6):663-70. DOI: 10.1038/ki.2010.484.
21. Ramaswami U, Parini R, Pintos-Morell G, Kalkum G, Kampmann C, Beck M, et al. Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey. Clin Genet. 2012;81(5):485-90. DOI: 10.1111/j.1399-0004.2011.01671.x.
22. Morel GP, Beck M. Fabry disease in children and the effects of enzyme replacement. Eur J Pediatr. 2009;168(11):1355-1363. DOI: 10.1007/s00431-009-0937-9
23. Gal A, Hughes DA, Winchester B. Toward a consensus in the laboratory diagnostics of Fabry disease - recommendations of a European expert group. J Inherit Metab Dis. 2011 Apr;34(2):509-14. DOI: 10.1007/s10545-010-9261-9.