Der undiagnostizierte Patient mit lysosomaler Speicherkrankheit

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

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