Zusammenfassung
Dieser Beitrag referiert den aktuellen Kenntnisstand in Diagnostik und Therapie der Hypophosphatasie (HPP), einer seltenen genetischen Erkrankung, die durch Mutationen im Gen der gewebeunspezifischen alkalischen Phosphatase (TNSALP) verursacht wird. Das klinische Spektrum der HPP zeigt eine große Variabilität und reicht von lebensbedrohlichen kindlichen Formen bis hin zu milden Formen mit Manifestation im Erwachsenenalter. Trotz der Seltenheit der Erkrankung ist die korrekte Diagnosestellung von außerordentlicher Wichtigkeit, wenn man den Patienten eine adäquate Therapie ermöglichen und potenzielle Komplikationen vermeiden möchte, so ist etwa bei der HPP die Anwendung von Bisphosphonaten kontraindiziert. Niedrige Serumspiegel der alkalischen Phosphatase (AP) sind das Hauptmerkmal der Erkrankung, aber für die Diagnosestellung häufig alleine nicht ausreichend, da einige weitere Erkrankungen ebenfalls eine Verminderung der AP bewirken können. Die Diagnose einer HPP kann bei Vorliegen typischer Symptome, einer laborchemisch erniedrigten AP und erhöhten AP-Substraten (Pyridoxalphosphat, anorganisches Pyrophosphat und Phosphoethanolamin) gestellt werden. Eine genetische Untersuchung des Gens ALPL kann die Diagnose in unklaren Fällen bestätigen. Seit 2015 besteht die Möglichkeit einer Enzymersatztherapie für die HPP mit Manifestation im Kindes- und Jugendalter. Trotzdem ist ein multimodaler und multidisziplinärer Therapieansatz mit regelmäßigen klinischen und laborchemischen Kontrollen ebenso Teil der Behandlung.
Abstract
This review presents the current knowledge on the diagnosis and treatment of hypophosphatasia, a rare genetic disease, caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene. The clinical spectrum of hypophosphatasia is highly variable ranging from lethal infantile forms to mild forms diagnosed in adults. Although the disease rarely occurs, correct diagnosis is important to provide appropriate treatment and to avoid worsening by use of harmful drugs such as bisphosphonates. Low serum values of alkaline phosphatase (ALP) is the main feature of HPP, but by itself not sufficient for diagnosis, as it can occur under different conditions. Diagnosis can be established by the combination of reduced levels of ALP, elevated ALP substrates (PLP, PEA, PPi) and typical symptoms and can be confirmed by genetic testing of ALPL mutations. Enzyme replacement therapy is now available for affected patients with onset of the disease during childhood and adolescence. Early results of enzyme replacement therapy are encouraging. However, a multidisciplinary approach remains the core of the treatment including nutritional support, monitoring of vitamin D, calcium and phosphate levels, physical therapy and regular dental care.
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F. Barvencik ist als Referent für die Firma Alexion tätig. T. Schmidt und M. Amling geben an, dass kein Interessenkonflikt besteht.
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Schmidt, T., Amling, M. & Barvencik, F. Hypophosphatasie. Internist 57, 1145–1154 (2016). https://doi.org/10.1007/s00108-016-0147-2
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DOI: https://doi.org/10.1007/s00108-016-0147-2