Zeitschrift für Rheumatologie

, Volume 65, Issue 1, pp 32–44 | Cite as

M. Gaucher, M. Fabry und Mukopolysaccharidose Typ I

Wie kann der Rheumatologe diese Patienten erkennen?
  • B. Manger
  • E. Mengel
  • R. M. Schaefer
  • C. Haase
  • J. Seidel
  • H. Michels
Übersichten

Zusammenfassung

Die lysosomalen Speichererkrankungen Morbus Gaucher, Morbus Fabry und MPS I zählen zu den seltenen erblichen Stoffwechselerkrankungen, die durch eine Enzymersatztherapie heute behandelbar sind. Damit durch eine frühzeitige Therapie sonst irreversible Komplikationen verhindern werden können, ist eine rechtzeitige Diagnosestellung wichtig. Weil Patienten mit diesen Speichererkrankungen wegen Symptomen von Seiten des muskuloskelettalen Systems nicht selten einen Rheumatologen aufsuchen können, sollte dieser die Symptome dieser seltenen Erkrankungen erkennen und einordnen können. Anhand von Kasuistiken zu M. Gaucher, M. Fabry und MPS I (hier M. Scheie) werden die Schlüsselsymptome diskutiert, die der Rheumatologe (Internist oder Pädiater) für die differenzialdiagnostische Abklärung dieser Patienten kennen sollte. Zusätzlich werden – neben einer kurzen Einführung in die Pathophysiologie – Hinweise zur Prognose und Therapie gegeben.

Schlüsselwörter

Lysosomale Speichererkrankungen M. Gaucher M. Fabry  Mukopolysaccharidose Typ I 

Gaucher disease, Fabry disease and mucopolysaccharidosis type I – How can the rheumatologist recognise these patients?

Summary

The lysosomal storage diseases Gaucher disease, Fabry disease and MPS I are rare inheritable metabolic disorders that are now treatable with enzyme replacement therapy. In order to avoid irreversible complications, an early diagnosis and initiation of therapy is important. Due to the musculoskeletal symptoms associated with these storage diseases, patients are likely to visit a rheumatologist, who should, therefore, be able to recognise and diagnose these rare diseases. On the basis of the causal factors behind Gaucher disease, Fabry disease und MPS I (here Scheie syndrome), key symptoms that the rheumatologist (internist or paediatrician) should be familiar with for the differential diagnosis of these patients will be discussed. In addition, a short introduction to the pathophysiology and data on the prognosis and therapy for these diseases will be presented.

Keywords

Lysosomal storage diseases Gaucher disease Fabry disease Mucopolysaccharidosis type I 

Notes

Interessenkonflikt:

Keine Angaben

Literatur

  1. 1.
    Aghion H (1934) La maladie de Gaucher dans l’enfance: forme cardiorenale. Paris: Faculte de Medecine de ParisGoogle Scholar
  2. 2.
    Allison JW, James CA, Arnold GL et al (1998) Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR. Pediatr Radiol 28:237–240CrossRefPubMedGoogle Scholar
  3. 3.
    Barton NW, Brady RO, Dambrosia JM et al (1991) Replacement therapy for inherited enzyme deficiency – macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 324:1464–1470PubMedGoogle Scholar
  4. 4.
    Brady RO, Kanfer JN, Shapiro D (1965) Metabolism of Glucocerebrosides. II. Evidence of an Enzymatic Deficiency in Gaucher’s Disease. Biochem Biophys Res Commun 18:221–225CrossRefPubMedGoogle Scholar
  5. 5.
    Brady RO, Gal AE, Bradley RM et al (1967) Enzymatic defect in Fabry’s disease. Ceramidetrihexosidase deficiency. N Engl J Med 276:1163–1167PubMedGoogle Scholar
  6. 6.
    Brady RO (1972) Lipidoses. Biochimie 54:723–733PubMedGoogle Scholar
  7. 7.
    Cleary MA, Wraith JE (1995) The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). Acta Paediatr 84:337–339PubMedGoogle Scholar
  8. 8.
    Cox T, Lachmann R, Hollak C et al (2000) Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355:1481–1485CrossRefPubMedGoogle Scholar
  9. 9.
    Desnick RJ, Ioannou Y, Eng CM (2001) Alpha-Galactosidase A deficiency: Fabry disease. In: Scriver C, Beaudet A, Sly W, Valle D (Hrsg) The Metabolic Basis of Inherited Disease. McGraw-Hill, New York, pp 3733–3774Google Scholar
  10. 10.
    Desnick RJ, Brady R, Barranger J et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138:338–346PubMedGoogle Scholar
  11. 11.
    Eng CM, Guffon N, Wilcox WR et al (2001) Safety and efficacy of recombinant human alpha-galactosidase A–replacement therapy in Fabry’s disease. N Engl J Med 345:9–16CrossRefPubMedGoogle Scholar
  12. 12.
    Fabry J (1898) Ein Beitrag zur Kenntnis der purpura haemorrhagica nodularis. Arch Dermatol Syph 43Google Scholar
  13. 13.
    Gaucher P (1882) De l’epithelioma primitif de la rate, hypertrophie idiopathique de la rate sans leucemie (doctoral thesis). ParisGoogle Scholar
  14. 14.
    Giraldo P, Pocovi M, Perez-Calvo J et al (2000) Report of the Spanish Gaucher’s disease registry: clinical and genetic characteristics. Haematologica 85:792–799PubMedGoogle Scholar
  15. 15.
    Hein LK, Hopwood JJ, Clements PR, Brooks DA (2003) The alpha-L-iduronidase mutations R89Q and R89W result in an attenuated mucopolysaccharidosis type I clinical presentation. Biochim Biophys Acta 1639:95–103PubMedGoogle Scholar
  16. 16.
    Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292PubMedGoogle Scholar
  17. 17.
    Hurler G (1919) Über einen Typ multipler Abartungen, vorwiegend am Skelettsystem. Z Kinderheilk 24:220CrossRefGoogle Scholar
  18. 18.
    Kauli R, Zaizov R, Lazar L et al (2000) Delayed growth and puberty in patients with Gaucher disease type 1: natural history and effect of splenectomy and/or enzyme replacement therapy. Isr Med Assoc J 2:158–163PubMedGoogle Scholar
  19. 19.
    Krivit W (2004) Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol 26:119–132CrossRefPubMedGoogle Scholar
  20. 20.
    MacDermot KD, Holmes A, Miners AH (2001) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38:769–775CrossRefPubMedGoogle Scholar
  21. 21.
    Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. Jama 281:249–254CrossRefPubMedGoogle Scholar
  22. 22.
    Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Valle D, Sly W (Hrsg) The metabolic and molecular basis of inherited disease. McGraw Hill, New York, pp 3421–3452Google Scholar
  23. 23.
    Niederau C, Rolfs A, vom Dahl S et al (2001) Diagnose und Therapie des Morbus Gaucher. Aktuelle Empfehlungen der deutschen Therapiezentren im Jahr 2000. Med Klin 96:32–39Google Scholar
  24. 24.
    Peters C, Balthazor M, Shapiro EG et al (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894–4902PubMedGoogle Scholar
  25. 25.
    Poll LW, Maas M, Terk MR et al (2002) Response of Gaucher bone disease to enzyme replacement therapy. Br J Radiol 75 Suppl 1:A25–36PubMedGoogle Scholar
  26. 26.
    Poorthuis BJ, Wevers RA, Kleijer WJ et al (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105:151–156PubMedGoogle Scholar
  27. 27.
    Rosenthal DI, Barton NW, McKusick KA et al (1992) Quantitative imaging of Gaucher disease. Radiology 185: 841–845PubMedGoogle Scholar
  28. 28.
    Scheie H, Hambrick G, Barness L (1962) A newly recognized forme fruste of Hurler’s disease (gargoylism). Am J Ophthalm 53:753–769Google Scholar
  29. 29.
    Shoenfeld Y, Gallant LA, Shaklai M et al (1982) Gaucher’s disease: a disease with chronic stimulation of the immune system. Arch Pathol Lab Med 106:388–391PubMedGoogle Scholar
  30. 30.
    Staba SL, Escolar ML, Poe M et al (2004) Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med 350:1960–1969CrossRefPubMedGoogle Scholar
  31. 31.
    Sweeley CC, Klionsky B (1963) Fabry’s Disease: Classification as a Sphingolipidosis and Partial Characterization of a Novel Glycolipid. J Biol Chem 238:3148–3150PubMedGoogle Scholar
  32. 32.
    Thurberg BL, Rennke H, Colvin RB et al (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62:1933–1946CrossRefPubMedGoogle Scholar
  33. 33.
    Vellodi A, Bembi B, de Villemeur TB et al (2001) Management of neuronopathic Gaucher disease: a European consensus. J Inherit Metab Dis 24:319–327CrossRefPubMedGoogle Scholar
  34. 34.
    Weidemann F, Breunig F, Beer M et al (2003) Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 108:1299–1301CrossRefPubMedGoogle Scholar
  35. 35.
    Wraith JE, Clarke LA, Beck M et al (2004) Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 144:581–588CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  • B. Manger
    • 1
  • E. Mengel
    • 2
  • R. M. Schaefer
    • 3
  • C. Haase
    • 4
  • J. Seidel
    • 5
  • H. Michels
    • 6
  1. 1.Universität Erlangen-NürnbergMedizinische Klinik IIIErlangenGermany
  2. 2.Universitäts-KinderklinikMainzGermany
  3. 3.UniversitätsklinikumMedizinische Klinik und Poliklinik DMünsterGermany
  4. 4.Klinikum der Friedrich-Schiller Universität JenaKlinik für Kinder- und JugendmedizinJenaGermany
  5. 5.SRH - Waldklinikum GeraKlinik für Kinder- und JugendmedizinGeraGermany
  6. 6.Rheumaklinik für Kinder und JugendlicheGarmisch-PartenkirchenGermany

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