Morbus Fabry

Der M. Fabry stellt eine X-chromosomal erbliche Speicherkrankheit dar, die viszerale Organe, das Nervensystem und die Blutgefäße befällt. Die Diagnose wird meist 5 – 15 Jahren nach Auftreten der ersten Symptome erst im Erwachsenenalter gestellt. Schmerzen der Hände und Füße, Hitze-
und Kälteintoleranz, Fieberschübe,vermindertes Schwitzen, Hornhauttrübung,blaurote Hautläsionen (Angiokeratome), Hornhauttrübung, Schlaganfall, linksventrikuläre Hypertrophie, Herzrhythmusstörungen, Depressionen Niereninsuffizienz sind die Symptome. Der Stoffwechseldefekt liegt im Katabolismus von Ceramiden (Glykosphingolipiden), die Komponenten verschiedener Organe darstellen. Durch die fehlende Aktivität der a-Galaktosidase kommt es bei Patienten mit M. Fabry zur Akkumulation eines bestimmten Glykosphingolipids, des Ceramid-Trihexosids, im Endothel von Gefäßen, Epithelien vieler Organe (besonders der Nieren) und Zellen der glatten Muskulatur. Das ubiquitäre Vorkommen der Speichersubstanzen erklärt die Manifestation der Erkrankung in vielen Organsystemen. Die Krankheit verläuft chronisch, erste Symptome sind Schmerzen und Parästhesien in den Extremitäten oft im Sinne von Minuten bis zu Tagen anhaltenden und qualvoll brennende Schmerzkrisen durch eine small-fibre-Neuropathie die auf durch Sphingolipid-Ablagerungen in den Vasa nervorum zurückgeführt wird, oft besteht eine Hypohidrosis. Pathognomonisch sind Angiokeratome (kleine, rötliche bis blauschwarze Gefäßektasien), woraus sich der Krankheitsname Angiokeratoma corporis diffusum ableitet. Im Erwachsenenalter manifestiert sich der M. Fabry am Herzen und den Nieren: Es können Herzrhythmusstörungen auftreten, häufig entwickelt sich eine Kardiomyopathie. Aufgrund einer Niereninsuffizienz werden die Patienten häufig dialysepflichtig. Auch zerebrovaskuläre Symptome insbesondere Schlaganfälle auch in jüngeren Jahren sowie begleitende kognitive Störungen werden beobachtet, Hörstörungen und Tinnitus, Abgeschlagenheit und Erschöpfung bei körperlicher Anstrengung, Depressionen, Schwindel und Kopfschmerzen kommen ebenfalls häufiger vor. Seit 2001 sind 2 i.v. Enzymersatztherapien mit α-GAL (Agalsidase α) in Europa zugelassen, das Ausmaße des Behandlungserfolgs ist noch nicht endgültig beurteilbar, ein Rückgang von Sphingolipid-Ablagerungen in den Organen ist aber belegt. Es ist davon auszugehen, das die Enzymersatztherapien nicht nur die Symptome bessern, sondern auch die Lebenserwartung verlängern.

 

Quellen / Literatur:

  1. Mehta, A, Clarke, J T R, Giugliani, R, Elliott, P, Linhart, A, Beck, M, Sunder-Plassmann, G, on behalf of the FOS Investigators, (2009). Natural course of Fabry disease: changing pattern of causes of death in FOS – Fabry Outcome Survey. J. Med. Genet. 46: 548-552 [Abstract] [Full Text]
  2. Schiffmann, R., Warnock, D. G., Banikazemi, M., Bultas, J., Linthorst, G. E., Packman, S., Sorensen, S. A., Wilcox, W. R., Desnick, R. J. (2009). Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant 24: 2102-2111 [Abstract] [Full Text]
  3. Oqvist, B., Brenner, B. M., Oliveira, J. P., Ortiz, A., Schaefer, R., Svarstad, E., Wanner, C., Zhang, K., Warnock, D. G. (2009). Nephropathy in Fabry disease: the importance of early diagnosis and testing in high-risk populations. Nephrol Dial Transplant 24: 1736-1743 [Full Text]
  4. Schoenmakere, G. D., Poppe, B., Wuyts, B., Claes, K., Cassiman, D., Maes, B., Verbeelen, D., Vanholder, R., Kuypers, D. R., Lameire, N., De Paepe, A., Terryn, W. (2008). Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients. Nephrol Dial Transplant 23: 4044-4048 [Abstract] [Full Text]
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  6. Invernizzi, P, Bonometti, M., Turri, E, Benedetti, M., Salviati, A (2008). A case of Fabry disease with central nervous system (CNS) demyelinating lesions: a double trouble?. Mult Scler 14: 1003-1006 [Abstract]
  7. Ortiz, A., Oliveira, J. P., Waldek, S., Warnock, D. G., Cianciaruso, B., Wanner, C., on behalf of the Fabry Registry, (2008). Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant 23: 1600-1607 [Abstract] [Full Text]
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  11. West, M., Nicholls, K., Mehta, A., Clarke, J. T.R., Steiner, R., Beck, M., Barshop, B. A., Rhead, W., Mensah, R., Ries, M., Schiffmann, R. (2009). Agalsidase Alfa and Kidney Dysfunction in Fabry Disease. J. Am. Soc. Nephrol. 20: 1132-1139 [Abstract] [Full Text]
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  18. Chimenti, C., Morgante, E., Tanzilli, G., Mangieri, E., Critelli, G., Gaudio, C., Russo, M. A., Frustaci, A. (2008). Angina in Fabry Disease Reflects Coronary Small Vessel Disease. Circ Heart Fail 1: 161-169 [Abstract] [Full Text]
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  20. Roach, E. S., Golomb, M. R., Adams, R., Biller, J., Daniels, S., deVeber, G., Ferriero, D., Jones, B. V., Kirkham, F. J., Scott, R. M., Smith, E. R. (2008). Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 39: 2644-2691 [Abstract] [Full Text]
  21. Invernizzi, P, Bonometti, M., Turri, E, Benedetti, M., Salviati, A (2008). A case of Fabry disease with central nervous system (CNS) demyelinating lesions: a double trouble?. Mult Scler 14: 1003-1006 [Abstract]
  22. Lavigne, M. D., Yates, L., Coxhead, P., Gorecki, D. C. (2008). Nuclear-targeted chimeric vector enhancing nonviral gene transfer into skeletal muscle of Fabry mice in vivo. FASEB J. 22: 2097-2107 [Abstract] [Full Text]
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  29. Terryn, W., Poppe, B., Wuyts, B., Claes, K., Maes, B., Verbeelen, D., Vanholder, R., De Boeck, K., Lameire, N., De Paepe, A., De Schoenmakere, G. (2008). Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population. Nephrol Dial Transplant 23: 294-300 [Abstract] [Full Text]
  30. Andrade, J., Waters, P. J., Singh, R. S., Levin, A., Toh, B.-C., Vallance, H. D., Sirrs, S. (2008). Screening for Fabry Disease in Patients with Chronic Kidney Disease: Limitations of Plasma {alpha}-Galactosidase Assay as a Screening Test. CJASN 3: 139-145 [Abstract] [Full Text]
  31. Ackerman, M. J., Landstrom, A. P. (2007). Detection of Subclinical Fabry Disease in Patients Presenting With Hypertrophic Cardiomyopathy. J Am Coll Cardiol 50: 2404-2405 [Full Text]
  32. Ries, M., Clarke, J. T., Whybra, C., Mehta, A., Loveday, K. S., Brady, R. O., Beck, M., Schiffmann, R. (2007). Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents. J Clin Pharmacol 47: 1222-1230 [Abstract] [Full Text]
  33. Tahir, H., Jackson, L. L., Warnock, D. G. (2007). Antiproteinuric Therapy and Fabry Nephropathy: Sustained Reduction of Proteinuria in Patients Receiving Enzyme Replacement Therapy with Agalsidase-beta. J. Am. Soc. Nephrol. 18: 2609-2617 [Full Text]
  34. Wanner, C., Breunig, F. (2007). Fabry Nephropathy and the Case for Adjunctive Renal Therapy. J. Am. Soc. Nephrol. 18: 2426-2428 [Full Text]
  35. Pastores, G. M., Boyd, E., Crandall, K., Whelan, A., Piersall, L., Barnett, N. (2007). Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 22: 1920-1925 [Abstract] [Full Text]
  36. Aerts, J. M., Groener, J. E., Kuiper, S., Donker-Koopman, W. E., Strijland, A., Ottenhoff, R., van Roomen, C., Mirzaian, M., Wijburg, F. A., Linthorst, G. E., Vedder, A. C., Rombach, S. M., Cox-Brinkman, J., Somerharju, P., Boot, R. G., Hollak, C. E., Brady, R. O., Poorthuis, B. J. (2008). Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc. Natl. Acad. Sci. USA 105: 2812-2817 [Abstract] [Full Text]
  37. Terryn, W., Poppe, B., Wuyts, B., Claes, K., Maes, B., Verbeelen, D., Vanholder, R., De Boeck, K., Lameire, N., De Paepe, A., De Schoenmakere, G. (2008). Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population. Nephrol Dial Transplant 23: 294-300 [Abstract] [Full Text]
  38. Andrade, J., Waters, P. J., Singh, R. S., Levin, A., Toh, B.-C., Vallance, H. D., Sirrs, S. (2008). Screening for Fabry Disease in Patients with Chronic Kidney Disease: Limitations of Plasma {alpha}-Galactosidase Assay as a Screening Test. CJASN 3: 139-145 [Abstract] [Full Text]
  39. Pastores, G. M., Boyd, E., Crandall, K., Whelan, A., Piersall, L., Barnett, N. (2007). Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 22: 1920-1925 [Abstract] [Full Text]
  40. Germain, D. P., Waldek, S., Banikazemi, M., Bushinsky, D. A., Charrow, J., Desnick, R. J., Lee, P., Loew, T., Vedder, A. C., Abichandani, R., Wilcox, W. R., Guffon, N. (2007). Sustained, Long-Term Renal Stabilization After 54 Months of Agalsidase beta Therapy in Patients with Fabry Disease. J. Am. Soc. Nephrol. 18: 1547-1557 [Abstract] [Full Text]
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Dr. Johannes Werle

Dr. med Johannes Werle

Redakteur