Skip to main content
SpringerLink
Log in

Morbus Gaucher, Mukopolysaccharidose Typ I (Scheie) und Morbus Fabry

Spezifisch therapierbare lysosomale Speicherkrankheiten und wichtige Differenzialdiagnosen zu entzündlich-rheumatischen Erkrankungen

Gaucher disease, mucopolysaccharidosis type I (Scheie disease) and Fabry disease

Lysosomal storage diseases treatable by specific therapies and the importance of differential diagnosis against inflammatory rheumatic diseases

  • Pädiatrie aktuell
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Für die lysosomalen Speichererkrankungen Morbus Gaucher (MG), Mukopolysaccharidose I-Scheie (MPS I-S) und Morbus Fabry (MF) stehen Enzymersatztherapien mit dem Potenzial einer Prognoseverbesserung zur Verfügung. Differenzialdiagnostisch sind u. a. rheumatische Erkrankungen abzugrenzen. Beim MG können Knochenschmerzen eine juvenile idiopathische Arthritis (JIA) vortäuschen; die Hepatosplenomegalie und die Panzytopenie lassen auch an Kollagenosen denken. Die MPS I-S kann u. a. wegen der Fingergelenkkontrakturen ebenfalls eine JIA imitieren. Beim MF müssen wegen der Schmerzen im Bereich von Händen und Füßen, ggf. verbunden mit Fieberschüben, wegen renaler und zerebrovaskulärer Ereignisse v. a. eine systemische JIA, aber auch Kollagenosen und Vaskulitiden ausgeschlossen werden. Bei kritischer Bewertung der klinischen Symptome der lysosomalen Speicherkrankheiten, der Labor- und apparativen Befunde sollten ein rechtzeitiges Erkennen dieser Erkrankungen als Voraussetzung für einen verbesserten Verlauf möglich und eine Verwechslung mit einer rheumatischen Differenzialdiagnose vermeidbar sein.

Abstract

Enzyme replacement therapies with the potential to improve prognosis are available for the lysosomal storage disorders Gaucher disease, mucopolysaccharidosis type I (MPS I-S; Scheie disease) and Fabry disease. Differential diagnosis is required to exclude a number of other conditions, including some rheumatic diseases. The bone pain associated with Gaucher disease can be misdiagnosed as juvenile idiopathic arthritis (JIA), and hepatosplenomegaly and pancytopenia may suggest collagen disorders. Symptoms such as contractures of the finger joints caused by Scheie disease can also imitate JIA. Fabry disease can also be confused with systemic JIA, collagen or vascular disorders, because of the pain it causes in hands and feet, sometimes associated with fever episodes, and renal and cerebrovascular symptoms. Critical evaluation of the clinical symptoms of lysosomal storage disorders in association with laboratory and test results should allow diagnosis of these diseases at an early stage, thereby facilitating better treatment and avoiding their misdiagnosis as any of several rheumatic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6
Abb. 7
Abb. 8

Literatur

  1. Meikle PJ, Hopwood JJ, Clague AE et al. (1999) Prevalence of lysosomal storage disorders. Jama 281: 249–254

    Article  PubMed  Google Scholar 

  2. Poorthuis BJ, Wevers RA, Kleijer WJ et al. (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105: 151–156

    PubMed  Google Scholar 

  3. Hollak CE, Levi M, Berends F et al. (1997) Coagulation abnormalities in type 1 Gaucher disease are due to low-grade activation and can be partly restored by enzyme supplementation therapy. Br J Haematol 96: 470–476

    Article  PubMed  Google Scholar 

  4. 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: 388–391

    PubMed  Google Scholar 

  5. Aguilera B, Ghauharali-van der Vlugt K, Helmond MT et al. (2003) Transglycosidase activity of chitotriosidase: improved enzymatic assay for the human macrophage chitinase. J Biol Chem 278: 40.911–40.916

    Article  Google Scholar 

  6. Boot RG, Verhoek M, De Fost M et al. (2004) Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Blood 103: 33–39

    Article  PubMed  Google Scholar 

  7. Beutler E, Gelbart T (1998) Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis 24: 2–8

    Article  PubMed  Google Scholar 

  8. Charrow J, Andersson HC, Kaplan P et al. (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160: 2835–2843

    Article  PubMed  Google Scholar 

  9. Zimran A, Kay A, Gelbart T et al. (1992) Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients. Medicine (Baltimore) 71: 337–353

    Google Scholar 

  10. Rosenthal DI, Barton NW, McKusick KA et al. (1992) Quantitative imaging of Gaucher disease. Radiology 185: 841–845

    PubMed  Google Scholar 

  11. 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: 1464–1470

    PubMed  Google Scholar 

  12. Charrow J, Andersson HC, Kaplan P et al. (2004) Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr 144: 112–120

    Article  PubMed  Google Scholar 

  13. 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: 32–39

    Google Scholar 

  14. 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: 1481–1485

    Article  PubMed  Google Scholar 

  15. Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Valle D et al. (eds) The metabolic and molecular basis of inherited disease. McGraw Hill, New York, pp 3421–3452

  16. Cleary MA, Wraith JE (1995) The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). Acta Paediatr 84: 337–339

    PubMed  Google Scholar 

  17. Hein LK, Hopwood JJ, Clements PR et al. (2003) The alpha-L-iduronidase mutations R89Q and R89 W result in an attenuated mucopolysaccharidosis type I clinical presentation. Biochim Biophys Acta 1639: 95–103

    PubMed  Google Scholar 

  18. Dumas HM, Fragala MA, Haley SM et al. (2004) Physical performance testing in mucopolysaccharidosis I: a pilot study. Pediatr Rehabil 7: 125–131

    Article  PubMed  Google Scholar 

  19. Braunlin EA, Stauffer NR, Peters CH et al. (2003) Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 92: 882–886

    Article  PubMed  Google Scholar 

  20. 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: 1960–1969

    Article  PubMed  Google Scholar 

  21. 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: 581–588

    Article  PubMed  Google Scholar 

  22. Wraith JE (2005) The first 5 years of clinical experience with laronidase enzyme replacement therapy for mucopolysaccharidosis I. Expert Opin Pharmacother 6: 489–506

    Article  PubMed  Google Scholar 

  23. Desnick RJ, Ioannou Y, Eng CM (2001) Alpha-Galactosidase A deficiency: Fabry disease. In: Scriver C, Beaudet A, Sly W et al. (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 3733–3774

  24. Desnick R, Ioannou Y, Eng C (2001) Alpha-galactosidase A deficiency: Fabry disease. In: Scriver CR, Sly WS, Beaudet AL (eds) The metabolic and molecular bases of inherited disease. McGraw Hill, New York, pp 2741–2784

  25. 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: 769–775

    Article  PubMed  Google Scholar 

  26. Ries M, Ramaswami U, Parini R et al. (2003) The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents. Eur J Pediatr 162: 767–772

    Article  PubMed  Google Scholar 

  27. Branton MH, Schiffmann R, Sabnis SG et al. (2002) Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore) 81: 122–138

    Google Scholar 

  28. 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: 338–346

    PubMed  Google Scholar 

  29. 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: 9–16

    Article  PubMed  Google Scholar 

  30. 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: 1933–1946

    Article  PubMed  Google Scholar 

  31. 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: 1299–1301

    Article  PubMed  Google Scholar 

  32. Mathies H, Truckenbrodt H, Sänger L et al. (1988) Diagnostische Kriterien der juvenilen chronischen Arthritis. EULAR, Basel

  33. Giannini EH, Brewer EJ (1987) Poor correlation between the erythrocyte sedimentation rate and clinical activity in juvenile rheumatoid arthritis. Clin Rheumatol 6: 197–201

    Article  PubMed  Google Scholar 

  34. Sherry DD (2004) Diagnose und Therapie von Schmerzverstärkungssyndromen bei Kindern: Erfahrung aus zwei Jahrzehnten. Aktuelle Rheumatol 29: 137–141

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kinderklinik Garmisch-Partenkirchen, Rheumaklinik für Kinder und Jugendliche/Allgemeinklinik, Gehfeldstraße 24, 82467 , Garmisch-Partenkirchen

    H. Michels

  2. Universitätskinderklinik Mainz

    E. Mengel

  3. Professor-Hess-Kinderklinik, Klinikum Bremen-Mitte gGmbH, Bremen

    H. I. Huppertz

  4. Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster

    R. M. Schaefer

Authors
  1. H. Michels
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Mengel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. I. Huppertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. M. Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Michels.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michels, H., Mengel, E., Huppertz, H.I. et al. Morbus Gaucher, Mukopolysaccharidose Typ I (Scheie) und Morbus Fabry. Monatsschr Kinderheilkd 154, 347–359 (2006). https://doi.org/10.1007/s00112-006-1324-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-006-1324-5

Schlüsselwörter

Keywords

Search

Navigation