Enfermedad de Fabry. Discapacitante y subdiagnosticada

  • Carmen Velázquez Arce Consultorio de Reumatología, Clínica Tajy, Encarnación, Paraguay. Gerente Médico para las Enfermedades Lisosomales del Laboratorio Genzyme en Paraguay
Palabras clave: Error Congénito del Metabolismo, Enfermedad de Fabry, Enzima Lisosomal, α-Galactosidasa A

Resumen

La enfermedad de Fabry se debe a un error congénito del metabolismo, que se produce por una mutación en el gen que codifica la enzima lisosomal α-Galactosidasa A. Se transmite por el cromosoma X, la incidencia varía según estudios de 1 en 400.000 a 1 en 117000 habitantes. La actividad deficiente de la enzima α-Galactosidasa A resulta en la acumulación de Globotriaosilaceramida (GL 3) dentro de los lisosomas, llevando al desarrollo de una cascada de eventos, siendo los tejidos más afectados el endotelio vascular y células del músculo liso, miocardio, células renales, células que componen el sistema nervioso. Los síntomas se manifiestan desde la infancia y muchas veces son confundidos con otras patologías más frecuentes, como Fiebre Reumática, Artritis Idiopática Juvenil, Síndrome de Raynaud, dolores del crecimiento, entre otros. El diagnóstico, en varones hemicigotas, se realiza mediante la cuantificación de la actividad de la enzima α-Galactosidasa A. Si es baja, confirma el diagnóstico. En mujeres heterocigotas, la actividad de la enzima puede ser normal, por lo que muchas veces es necesario el estudio molecular del ADN. La terapia de reemplazo enzimático ha demostrado revertir los síntomas y disminuir el número de eventos mayores principalmente cuando es iniciada en etapas precoces de la enfermedad.

Citas

(1) Anderson W: A case of “Angeio-keratoma”. Br J Dermatol. 1898;10:113-117.

(2) G ermain DP. Fabry Disease. Orphanet Journal of Rare Diseases. 2010:5-30.

(3) Weidemann F, Kramer J: Patiens with Fabry Disease after Enzyme Replacement Therapy. Dose Reduction Versus Treatment Switch. J Am SocNephrol. 2014;25:837-849.

(4) Poorthuis BJ, Wevers RA, Kleijer JW, Groener JE, De Jong JG. The frequency of lysosomal storage diseases in The Netherlands. Hum G enet. 1999:105(1–2):151–56.

(5) Meikle PJ, Hopwood JJ, Clague AE, Carrey WF: Prevalence of lysosomal storage disorders. JAMA. 1999;281:249-54.

(6) Kotanko P, Kramar R, Devrnja D, et al. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am SocNephrol. 2004;15:1323–29.

(7) Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, Kanzaki T, Enriquez AL, Eng CM, Tanaka H, Tei C, Desnick RJ. Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype. Kidney Int. 2003;64:801–7.

(8) Brouns R, Thijs V, Eyskens F, Van den Broeck M, Belachew S, Van Broeckhoven C, et al. Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. Stroke. 2010;41:863–8.

(9) Rolfs A, Bottcher T, Zschiesche M, et al. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005;366:1794–96.

(10) Nakao S, Takenaka T, Maeda M. et al. An atypical variant of Fabry‘s disease in men with left ventricular hypertrophy. N Engl J Med. 1995 Aug 3;333(5):288-93.

(11) Rima E, Divya S, John D. Fabry Disease. Journal of the Neurological Sciences. 2014;344:5–19.

(12) Zarate Y. A, Hopkin R. J. Lisosomal Storage Disease. Fabry Disease. Lancet. 2008;372:1427-35.

(13) Sachdev B, Takenaka T, Teraguchi H, Tei C. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation. 2002;105(12):1407-11.

(14) Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Investig. 2004;34(3):236–42.

(15) 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;162:767–72.

(16) L inhart A, Kampmann C, Zamorano JL. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;(28):1228–35.

(17) Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43.

(18) 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):361–6.

(19) Deshayes S, Auboire L, Jaussaud R, el al. Prevalence of Raynaud Phenomenon and NailfoldCapillaroscopic Abnormalities in Fabry Disease. Medicine. 2015(94);20:1-5.

(20) E llaway C. Diagnostic dilemma and delay in Fabry disease: Insights from a case series of young female patients. Journal of Paediatrics and Child Health. 2015;(51):369–72.

(21) L acomis D, Roeske L, Andrson L, et al. Neuropathy and Fabry´s Disease. Muscle Nerve. 2005;( 31):102–7.

(22) Rosenmann E, Kobrin I, Cohen T. Kidney involvement in systemic lupus erythematosus and Fabry’s disease. Nephon. 1983;34:180–4.

(23) Rahman P, Gladman DD, Wither J, Silver MD. Coexistence of Fabry‘s disease and systemic lupus erythematosus. Clin Exp Rheumatol. 1998;16:475-8.

(24) Arias Martínez N, Barbado Hernández FJ, Pérez Martín G, et al. E nfermedad de Fabry asociada a artritis reumatoide: Una encrucijada multisistémica. An Med Interna. (Madrid) 2003;(20)1:36-8.

(25) Donaghy M, Hakin RN, Bamford JM, Garner A, Kirkby GR, Noble BA, et al. Hereditary sensory neuropathy with neurotrophic keratitis. Description of an autosomal recessive disorder with a selective reduction of small myelinated nerve fibres and a discussion of the classification of the hereditary sensory neuropathies. Brain. 1987;(110)3:563–83.

(26) McDougall AJ, McLeod JG. Autonomic neuropathy. Clinical features, investigation, pathophysiology, and treatment. J Neurol Sci. 1996;(137)2:79–88.

(27) L idove O, Ramaswami U, Jaussaud R, Barbey F, et al. Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey.

Int J Clin Pract. 2006;60:1053–9.

(28) L inhart A, Kampmann C, Zamorano JL, Sunder-Plassmann G, Beck M, Mehta A, Elliott PM. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;28:1228–35.

(29) Cable W.J, Kolodny E.H, Adams R.D. Fabry disease: impaired autonomic function. Neurology. 1982;(5)32: 498–502.

(30) Fukuhara N, Suzuki M, Fujita N, et al. Fabry‘s disease on the mechanism of the peripheral nerve involvement. Acta Neuropathol. 1975;(1)33:9–21.

(31) L ao LM, Kumakiri M, Mima H, Kuwahara H, Ishida H, Ishiguro K, et al. The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis. J Dermatol Sci. 1998;(2)18:109–17.

(32) Mutoh T, Senda Y, Sugimura K, et al. Severe orthostatic hypotension in a female carrier of Fabry‘s disease. Arch Neurol. 1988;(4)45:468–72.

(33) Orteu CH, Jansen T, Lidove O, Jaussaud R, et al. Fabry disease and the skin: data from FOS, the Fabry outcome survey. Br JDermatol. 2007;157:331–3.

(34) Zampetti A, Orteu CH, Antuzzi D, Bongiorno MR, et al. Interdisciplinary Study Group on Fabry Disease (ISGF). Angiokeratoma: decision-making aid for the diagnosis of Fabry disease. Br J Dermatol. 2012;166:712–20.

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

(36) Wanner C, Oliveira J. P, Ortiz A, Mauer M, et al. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry registry. Clin J Am Soc Nephrol. 2010;(12):2220–8.

(37) G runfeld JP, Lidove O, Joly D, Barbey F. Renal disease in Fabry patients. J Inherit Metab Dis 2001;24:71–4.

(38) Sessa A., Meroni M, Battini G, Maglio A, Brambilla PL, Bertella M, et al. Renal pathological changes in Fabry disease. J Inherit Metab Dis. 2001;24:66–70.

(39) Banikazemi M, Bultas J, Waldek S, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007;146:77–86.

(40) Schiff Mann R. Enzyme replacement in Fabry disease: the essence is in the kidney. Ann Intern Med. 2007;146:142–44.

(41) E ng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006;8:539–48.

(42) Shah JS, Elliott PM. Fabry disease and the heart: An overview of the natural history and the effect of enzyme replacement therapy. Acta Paediatr Suppl 2005;94:11–4 (discussion). Shah JS, Elliott PM. Fabry disease and the heart: An overview of the natural history and the effect of enzyme replacement therapy. Acta Paediatr Suppl. 2005;94:9–10.

(43) E lliott PM, Kindler H, Shah JS, Sachdev B, Rimoldi OE, et al: Coronary microvascular dysfunction inmale patients with Anderson-Fabry disease and the effect of treatmentwith alpha galactosidase A. Heart. 2006;92:357-60.

(44) Palecek T, Dostalova G, Kuchynka P, Karetova D, Bultas J, Elleder M, Linhart A: Right ventricular involvement in Fabry disease. J Am Soc Echocardiogr 2008;21:1265-8.

(45) T akenaka T, Teraguchi H, Yoshida A, Taguchi S, Ninomiya K, Umekita Y, et al. Terminalstage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study. J Cardiol 2008;51(1):50–9.

(46) Fellgiebel A, Muller MJ, Ginsberg L: CNS manifestations of Fabry’s disease. Lancet Neurol 2006;5:791-5.

(47) Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke 2009;40:788-94.

(48) G insberg L, Manara R, Valentine AR, Kendall B, Burlina AP. Magnetic resonance imaging changes in Fabry disease. Acta Paediatr Suppl 2006;95:57–62.

(49) Ries M, Kim HJ, Zalewski CK, Mastroianni MA, Moore DF, Brady RO,Dambrosia JM, Schiffmann R, Brewer CC. Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease. Brain 2007;130:143-50.

(50) Falke K, Buttner A, Schittkowski M, Stachs O, Kraak R, Zhivov A, Rolfs A, Guthoff R: The microstructure of cornea verticillata in Fabry disease and amiodarone-induced keratopathy: a confocal laser-scanning microscopy study. Graefes Arch Clin Exp Ophthalmol 2009;247:523-34.

(51) Falke K, Buttner A, Schittkowski M, Stachs O, Kraak R, Zhivov A, Rolfs A, Guthoff R: The microstructure of cornea verticillata in Fabry disease and amiodarone-induced keratopathy: a confocal laser-scanning microscopy study. Graefes Arch Clin Exp O phthalmol. 2009;247:523-534.

(52) Utsumi K, Yamamoto N, Kase R, et al. High incidence of thrombosis in Fabry’s disease. Intern Med. 1997;36:327–9.

(53) Ramaswami U, Whybra C, Parini R, et al. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr. 2006;95:86–92.

(54) Hoffman B, Martin S, Atul M, et al Gastrointestinal Symptoms in 342 Patients With Fabry Disease: Prevalence and Response to E nzyme Replacement Therapy. Clinical Gastroenterology and hepatology. 2007;5:1447–53.

(55) Magage S, Lubanda JC, Susa Z, Bultas J, Karetova D, Dobrovolny R, Hrebicek M, Germain DP, Linhart A. Natural history of the respiratory involvement in Anderson-Fabry disease. J InheritMetab-Dis. 2007;30:790–9.

(56) Mersebach H, Johansson JO, Rasmussen AK, Bengtsson BA, Rosenberg K, Hasholt L,et al. Osteopenia: a common aspect of Fabry disease. Predictors of bone mineraldensity. Genet Med. 2007;9(12):812–8.

(57) Horiuchi H, Saito N, Kobayashi S, et al.Avascular Necrosis of the Femoral Head in a Patient With Fabry’s Disease Identification of CeramideTrihexoside in the Bone by Delayed-Extraction Matrix-Assisted Laser Desorption Ionization–Time-of-Flight Mass Spectrometry. Arthritis & Rheumatism. 2002; 46(7):1922-25.

(58) Cole AL, Lee PJ, Hughes DA, Deegan PB, Waldek S, Lachmann RH. Depression in adults with Fabry disease: a common and under-diagnosed problem. J InheritMetabDis. 2007;30:943–51.

(59) Deegan PB, Baehner AF, Barba Romero MA, Hughes DA, Kampmann C, Beck M. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet. 2006;43:347–52.

(60) Mayes JS, Scheerer JB, Sifers RN, Donaldson ML: Differential assay for lysosomal alpha-galactosidases in human tissues and its application to Fabry’s disease. ClinChimActa. 1981,112:247-251.

(61) Ceci R, FrancescoP, Mucci J, et al. Reliability of enzyme assays in dried blood spots for diagnosis of 4 lysosomal storage disorders. Advances in Biological Chemistry. 2011;1:58-64.

(62) Mehta A, Clarke JT, Giugliani R, Elliott P, Linhart A, Beck M, et al. Natural course of Fabry disease: changing pattern of causes of death in FOS — Fabry Outcome Survey. J Med Genet.

;46(8):548–52.

(63) Amartino H, Politei J, Cabrera G, et al. Guía práctica para el estudio, diagnóstico y tratamiento de la Enfermedad de Fabry. www.intramed.net

(64) Lenoir G, Rivron M, Gubler MC, Dufier JL, Tome FS, Guivarch M. Fabry‘s disease. Carbamazepinetherapy in acrodyniform syndrome. Arch Fr Pediatr. 1977;34(8):704–16.

(65) Desnick R. Enzyme replacement therapy for Fabry disease: lesson from two α-galatosidaseA orphan products and one FDA approval. E xpert Opin Biol Ther. 2004;4(7):1167-76.

Publicado
2016-03-04
Cómo citar
Velázquez Arce, C. (2016). Enfermedad de Fabry. Discapacitante y subdiagnosticada. Revista Paraguaya De Reumatología, 1(2), 99-106. Recuperado a partir de http://revista.spr.org.py/index.php/spr/article/view/22
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