Therapie und Management der Hypophosphatasie im Erwachsenenalter: Differenzierte Therapieansätze in Abhängigkeit vom Krankheitsverlauf

Zusammenfassung

Die Hypophosphatasie (HPP) ist eine genetisch bedingte Systemerkrankung, die durch eine verminderte Aktivität der gewebsunspezifischen alkalischen Phosphatase (TNSALP) gekennzeichnet ist. Die daraus resultierende Akkumulation ihrer Substrate führt zu einer beeinträchtigten Knochenmineralisation und kann daneben muskuläre, neurologische, gastrointestinale sowie unspezifische systemische Beschwerden verursachen. Bei Erwachsenen reicht das klinische Spektrum von chronischen Schmerzen, Fatigue und eingeschränkter Muskelkraft bis hin zu Pseudofrakturen und im Einzelfall verzögerter Frakturheilung; zugleich sind asymptomatische Verläufe trotz genetischer Variante möglich. Mit Asfotase alfa steht seit 2015 erstmals eine kausale Therapie für Betroffene mit pädiatrischem Krankheitsbeginn und signifikanter Skelettmanifestation zur Verfügung. Sie verbessert die Knochenmineralisation und Frakturheilung und führt damit zu einer Steigerung von Mobilität, körperlicher Leistungsfähigkeit und Lebensqualität. Mildere oder spätmanifeste Verläufe erfordern hingegen überwiegend ein multimodales, symptom- und funktionsorientiertes Management, das gezielte Physiotherapie, physikalische Maßnahmen und eine strukturierte Schmerztherapie umfasst. Osteoanabole Strategien können bei begleitender Osteoporose erwogen werden, sind jedoch nicht zur Behandlung der Grunderkrankung etabliert. Operative Eingriffe sollten aufgrund der eingeschränkten Knochenqualität nur nach sorgfältiger Planung und metabolischer Vorbereitung erfolgen, um Komplikationen zu minimieren. Insgesamt ist ein interdisziplinäres, individuell abgestimmtes Therapiekonzept entscheidend, um Funktion, Mobilität und Lebensqualität erwachsener HPP-Betroffener langfristig zu erhalten.

Abstract

English: Hypophosphatasia (HPP) is a genetically determined systemic disorder characterized by reduced activity of tissue-nonspecific alkaline phosphatase (TNSALP). The resulting accumulation of its unhydrolyzed substrates leads to impaired bone mineralization and may also cause muscular, neurological, gastrointestinal or nonspecific systemic symptoms. In adults, the condition may present with chronic pain, fatigue, reduced muscle strength, pseudofractures or, in some cases, delayed fracture healing, while asymptomatic courses may occur despite detectable genetic variants. Since 2015, asfotase alfa has been available as the first causal therapy for patients with pediatric-onset HPP and significant skeletal involvement, improving bone mineralization, fracture healing, mobility and quality of life. In contrast, mild or late-onset forms predominantly require multimodal, symptom-oriented management, including physiotherapy, physical medicine interventions and structured pain therapy. Osteoanabolic treatment strategies may be considered only in cases of concomitant osteoporosis and are not established options for treating the underlying disease. Surgical procedures require careful preoperative planning and metabolic optimization due to impaired mineralization. Overall, the long-term management of adults with HPP relies on a coordinated, interdisciplinary approach to maintain function, mobility and health-related quality of life.

Schlüsselwörter

Hypophosphatasie - Enzymersatztherapie - Alkalische Phosphatase - ALPL Variante

Key words

Hypophophatasia - enzyme replacement therapy - ALPL variants - Alkaline Phosphatase

Publication History

Article published online:
13 February 2026

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