Der undiagnostizierte Patient mit lysosomaler Speicherkrankheit

H. Michels

doi:10.1055/s-0037-1618201

Arthritis und Rheuma, Table of Contents

Arthritis und Rheuma 2013; 33(06): 386-392
DOI: 10.1055/s-0037-1618201

Alltägliches in der kinderrheumatologischen Praxis?

Schattauer GmbH

Der undiagnostizierte Patient mit lysosomaler Speicherkrankheit

Wie lässt sich die „Nadel im Heuhaufen“ finden?The undiagnosed patient with a lysosomal storage diseaseHow to find the needle in the haystack?

Authors

H. Michels

Abstract

Zusammenfassung

Die lysosomalen Speicherkrankheiten (LSK) umfassen eine Gruppe von etwa 50 monogenen, autosomal-rezessiv oder X-chromosomal (3) vererbten Erkrankungen mit gleichem Pathomechanismus, aber teils sehr unterschiedlicher Symptomatik. Die Verläufe sind häufig schwerwiegend mit dubiöser Prognose. Aufgrund eines mutationsbedingten Funktionsverlustes lysosomaler Enzyme werden bestimmte Makromoleküle nicht abgebaut, sondern gespeichert, mit der Folge von Gewebe- und Organschädigung. Bei derzeit sechs LSK stehen seit geraumer Zeit Enzymersatztherapien zur Verfügung mit dem Potenzial einer deutlichen Prognoseverbesserung bei rechtzeitigem Therapiebeginn vor Manifestation irreversibler Veränderungen. Wegen der Beteiligung des Bewegungsapparates bei einem Teil der LSK gehören (Kinder-)Rheumatologen und Orthopäden häufig zu den erstkonsultierten Ärzten. In der täglichen Routine stellen insbesondere die attenuierten Formen eine diagnostische Herausforderung dar. Die vorliegende Arbeit gibt praktische Hinweise, wie das wichtige Ziel einer rechtzeitigen Diagnosestellung erreicht werden kann.

Summary

Lysosomal storage disorders (LSD) comprise a group of about 50 autosomal-recessive or X-linked (3) inherited, metabolic diseases with heterogeneous clinical pictures despite of the same pathomechanism. The mutations lead to defective lysosomal enzymes resulting in loss of their function. As a consequence, macromolecules which are normally degraded in the lysosomes accumulate, thus injuring tissues and organs throughout the body. Therefore, the LSDs have a broad clinical spectrum with a doubtful prognosis and shortened life span. For six LSDs enzyme replacement therapies (ERT) are available and may markedly improve the outcomes provided ERT is given before irreversible damages have developed. Since a number of LSDs exhibit various musculoskeletal manifestations, (pediatric) rheumatologists and orthopedists belong to the first contacted physicians. This implies a great challenge for them to make the correct diagnosis in daily routine, especially with respect to the attenuated LSD forms. The aim of this paper is to provide some helpful hints and clues to arrive at an early diagnosis.

Schlüsselwörter

Lysosomale Speicherkrankheiten - Bewegungsapparat - Enzymersatztherapie

Keywords

Lysosomal storage diseases - musculoskeletal system - enzyme replacement therapy

Full Text

References

Literatur
1 Meikle PJ, Fietz MJ, Hopwood JJ. Diagnosis of lysosomal storage disorders: current techniques and future directions. Expert Rev Mol Diagn 2004; 4 (05) 677-691.
2 Meikle PJ, Ranieri E, Simonsen H. et al. Newborn screening for lysosomal storage disorders: clinical evaluation of a two-tier strategy. Pediatrics 2004; 114 (04) 909-916.
3 Platt FM, Boland B, van der Spoel AC. The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol 2012; 199 (05) 723-734.
4 Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 2006; 91 (11) 896-899.
5 Saftig P, Klumperman J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 2009; 10 (09) 623-635.
6 van Gelder CM, Vollebregt AA, Plug I. et al. Treatment options for lysosomal storage disorders: developing insights. Expert Opin Pharmacother 2012; 13 (16) 2281-2299.
7 Gieselmann V. Cellular pathophysiology of lysosomal storage diseases. In: Mehta A, Beck M, Sunder-Plassmann G. eds. Fabry disease. Perspectives from 5 years of FOS. Oxford: PharmaGenesis^TM Ltd; 2006: 33-43.
8 Lachmann RH. Enzyme replacement therapy for lysosomal storage diseases. Curr Opin Pediatr 2011; 23 (06) 588-593.
9 Michels H, Mengel E, Huppertz H, Schaefer R. Morbus Gaucher, Mukopolysaccharidose Typ I (Scheie) und Morbus Fabry. Spezifisch therapierbare lysosomale Speicherkrankheiten und wichtige Differenzialdiagnosen zu entzündlich-rheumatischen Erkrankungen. Monatsschr Kinderheilk 2006; 154 (04) 347-359.
10 Manger B. Lysosomale Speicherkrankheiten. Z Rheumatol 2010; 69 (06) 527-538.
11 Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology (Oxford) 2011; 50 (Suppl. 05) v19-v25.
12 Cimaz R, Coppa GV, Kone-Paut I. et al. Joint contractures in the absence of inflammation may indicate mucopolysaccharidosis. Pediatr Rheumatol Online J 2009; 7: 18.
13 Chen SJ, Li YW, Wang TR, Hsu JC. Bony changes in common mucopolysaccharidoses. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1996; 37 (03) 178-184.
14 White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology (Oxford) 2011; 50 (Suppl. 05) v26-v33.
15 Van Meir N, De Smet L. Carpal tunnel syndrome in children. Acta Orthop Belg 2003; 69 (05) 387-395.
16 Thomas JA, Beck M, Clarke JT, Cox GF. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. J Inherit Metab Dis 2010; 33 (04) 421-427.
17 Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol 2006; 51 (01) 1-17.
18 Schöpfer K, Miebach E, Beck M, Pitz S. Lysosomale Speichererkrankungen – Update und neue therapeutische Optionen. Klin Monatsbl Augenheilkd 2011; 228 (02) 144-160.
19 vom Dahl S, Mengel E. Lysosomal storage diseases as differential diagnosis of hepatosplenomegaly. Best Pract Res Clin Gastroenterol 2010; 24 (05) 619-628.
20 Imundo L, Leduc CA, Guha S. et al. A complete deficiency of Hyaluronoglucosaminidase 1 (HYAL1) presenting as familial juvenile idiopathic arthritis. J Inherit Metab Dis 2011; 34 (05) 1013-1022.
21 Burlina AP, Sims KB, Politei JM. et al. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel. BMC Neurol 2011; 11: 61.
22 Linhart A, Palecek T, Bultas J. et al. New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J 2000; 139 (06) 1101-1108.
23 Buechner S, Moretti M, Burlina AP. et al. Central nervous system involvement in Anderson-Fabry disease: a clinical and MRI retrospective study. J Neurol Neurosurg Psychiatry 2008; 79 (11) 1249-1254.
24 Sodi A, Ioannidis AS, Mehta A. et al. Ocular manifestations of Fabry’s disease: data from the Fabry Outcome Survey. Br J Ophthalmol 2007; 91 (02) 210-214.
25 Germain DP. General aspects of X-linked diseases. In: Mehta A, Beck M, Sunder-Plassmann G. editors. Fabry disease. Perspectives from 5 years of FOS. Oxford: PharmaGenesis™ Ltd; 2006: 63-68.
26 Gupta S, Ries M, Kotsopoulos S, Schiffmann R. The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 2005; 84 (05) 261-268.
27 MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001; 38 (11) 769-775.
28 Bekri S. Laboratory diagnosis of lysosomal storage diseases. In: Mehta A, Beck M, Sunder-Plassmann G. eds. Fabry disease. Perspectives from 5 years of FOS. Oxford: PharmaGenesis™ Ltd: 2006: 69-74.
29 Laney DA, Bennett RL, Clarke V. et al. Fabry disease practice guidelines: recommendations of the national society of genetic counselors. J Genet Couns 2013; 22 (05) 555-564.
30 Beck M. Therapy for lysosomal storage disorders. IUBMB Life 2010; 62 (01) 33-40.
31 Ohashi T. Enzyme replacement therapy for lysosomal storage diseases. Pediatr Endocrinol Rev 2012; 10 (Suppl. 01) 26-34.
32 Parenti G, Pignata C, Vajro P, Salerno M. New strategies for the treatment of lysosomal storage diseases (review). Int J Mol Med 2013; 31 (01) 11-20.
33 Urbanelli L, Magini A, Polchi A. et al. Recent developments in therapeutic approaches for lysosomal storage diseases. Recent Pat CNS Drug Discov 2011; 6 (01) 1-19.
34 Michels H, Mengel E. Lysosomal storage diseases as differential diagnoses to rheumatic disorders. Curr Opin Rheumatol 2008; 20 (01) 76-81.
35 Fuller M, Meikle PJ, Hopwood JJ. Epidemiology of lysosomal storage diseases: an overview. In: Mehta A, Beck M, Sunder-Plassmann G. eds. Fabry disease. Perspectives from 5 years of FOS. Oxford: PharmaGenesis™ Ltd; 2006: 9-20.