Hypophosphatasie

R. Hennings; A. Roth; L. Seefried

doi:10.1055/s-0038-1675660

Osteologie, Table of Contents

Osteologie 2018; 27(04): 200-207
DOI: 10.1055/s-0038-1675660

Seltene Knochenerkrankungen

Georg Thieme Verlag KG Stuttgart · New York

Hypophosphatasie

Eine seltene Erkrankung des KnochenstoffwechselsHypophosphatasiaA rare disease of bone metabolism

R. Hennings

¹Klinik und Poliklinik für Orthopädie, Unfallchirurgie und Plastische Chirurgie, Universitätsklinikum Leipzig

,

A. Roth

¹Klinik und Poliklinik für Orthopädie, Unfallchirurgie und Plastische Chirurgie, Universitätsklinikum Leipzig

,

L. Seefried

²Klinische Studieneinheit, Universität Würzburg, Orthopädische Klinik – König-Ludwig-Haus, Würzburg

› Author Affiliations

Abstract

Zusammenfassung

Die Hypophosphatasie (HPP) ist eine seltene, vererbbare Erkrankung mit Beteiligung des Knochen- und Mineralstoffwechsels. Verursachende Mutationen des ALPL-Gens (OMIM 171760) führen zu einer gestörten Aktivität der gewebeunspezifischen alkalischen Phosphatase (TNAP), welche eine entscheidende Funktion in der Skelettmineralisation hat. Die im Serum gemessene alkalische Phsophatase (AP) setzt sich zu 90 % aus der TNAP zusammen und stellt den laborchemischen Leitparameter dar. Erhöhte Serumkonzentrationen der Substrate der TNAP, insbesondere Phyridoxal- 5`-Phosphat (PLP) unterstützen die Diagnostik. Die Diagnosesicherung kann mittels molekulargenetischer Analyse des ALPL-Gens erfolgen. Anhand des Manifestationsalters werden mehrere Formen (perinatale, infantile, kindliche und adulte odonto-HPP) unterschieden. Eine Unterscheidung der Formen ist oft nicht sicher möglich. Neben dem Skelettapparat können zahlreiche Organsysteme (ZNS, Lunge, Gastrointestinaltrakt, Nieren) betroffen sein, sodass die HPP als metabolische Multisystemerkrankung gewertet werden sollte. Schwere kindliche Formen sind mit einer hohen Morbidität und Mortalität verbunden. Eine kurative Therapie steht aktuell nicht zur Verfügung. Bei allen Manifestationsformen zielen die therapeutischen Maßnahmen auf eine Verbesserung der krankheitsassoziierten Symptome und Vermeidung von Komplikationen. Seit 2015 steht mit dem rekombinanten Enzym Asfotase alfa (Strensiq^®) ein Präparat zur Enzymersatztherapie für HPP-Formen mit nachgewiesener Erstmanifestation im Kindesalter zur Therapie der Skelettmanifestation zur Verfügung.

Summary

Hypophosphatasia (HPP) is a rare inherited disease with involvement of bone and mineral metabolism. Mutations of the ALPL gene (OMIM 171760) result in a decreased activity of the tissue-unspecific alkaline phosphatase (TNAP), which has a crucial function in skeletal mineralization. The alkaline phsophatase (AP) measured in serum consists out of 90 % TNAP and represents the keybiomarker. Increased serum concentrations of TNAP substrates, in particular phyridoxal-5`-phosphate (PLP), are useful for diagnostics. The diagnosis can be confirmed by molecular genetic analysis. Based on the age of the manifestation, several forms are distinguished (perinatal, infantile, infantile and adult odonto- HPP), whereby a differentiation of the forms is often not reliable. In addition to the skeletal manifestation, numerous organ systems (CNS, lungs, gastrointestinal tract, kidneys) can be affected. Therefore, HPP should be considered as a multi-system disease. At the moment there is no curative therapy available. The therapies aim to improve disease-associated symptoms and avoid complications. Since 2015, the recombinant enzyme Asfotase alfa (Strensiq^®) has been available for enzyme replacement therapy for HPP forms with verified first manifestation in childhood and skeletal manifestation.

Schlüsselwörter

Hypophosphatasie - alkalische Phosphatase - ALPL-Gen

Keywords

Hypophosphatasia - alkaline phosphatase - ALPL gene

Full Text

References

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