The Global Hypophosphatasia Registry: lessons learned from a decade of real-world data.

INTRODUCTION: Hypophosphatasia (HPP) is an inherited, metabolic, rare disease characterized by a high level of clinical heterogeneity. In response to this robust heterogeneity, the Global HPP Registry was formed to characterize the types of manifestations that patients may experience, as well as to compile information on genetic underpinnings of the disease, overall impact on patient quality of life, and safety and effectiveness of enzyme replacement therapy. The objective of this review was to synthesize key learnings gained from the Global HPP Registry, which is now in its tenth year of enrolling patients. METHODS: Registry data were analyzed to provide up-to-date information on age at diagnosis of HPP and alkaline phosphatase substrate testing. Published articles and abstracts reporting results from the registry were reviewed and summarized. RESULTS: Analyses showed peaks in age at diagnosis of HPP in early childhood and middle adulthood. Pyridoxal 5'-phosphate testing was performed in 18% to 61% of registry patients across geographic regions, and phosphoethanolamine testing was performed in 5% to 48% of registry patients. Published reports demonstrate that nonskeletal manifestations of HPP are an important disease feature that can affect functional outcomes. The review also reports recent findings on the genetics of HPP across a broad patient population, including heterozygous patients, and integrated literature showing that patients with HPP can have high levels of disease burden regardless of whether they present with overt skeletal manifestations or if the disease first presents in childhood or adulthood. Based on the collective findings of this review, an updated classification system for patients with HPP is proposed that incorporates a more recent understanding of the spectrum of this condition. Outcomes showing the effectiveness of enzyme replacement therapy among children and adults treated in a real-world setting are also included. CONCLUSIONS: In summary, learnings from the past decade of the registry have improved the overall understanding of HPP in a wide patient population and may play an important role in improving disease recognition and diagnosis.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics