Burden of disease in US patients with skeletal versus muscular or pain manifestations of hypophosphatasia: An analysis from the Global HPP Registry.

BACKGROUND: Hypophosphatasia (HPP) is a metabolic disorder characterized by deficient alkaline phosphatase (ALP) activity, defective mineralization of bones and teeth, and non-skeletal manifestations. We compared disease burden between patients with skeletal and non-skeletal manifestations. METHODS: Data from US adults enrolled in the Global HPP Registry through July 2024 were analyzed to compare baseline characteristics, genetic testing results, functional outcomes, and patient-reported outcomes between participants with and without overt skeletal manifestations. Patients who had only dental manifestations were excluded. RESULTS: Of 283 participants, 234 (82.7%) had skeletal manifestations (79.1% female; 89.3% White; median age 48.7 years) and 49 (17.3%) had only non-skeletal manifestations (69.4% female; 83.7% White; median age 41.5 years) at baseline. Muscular/pain symptoms were reported in 79.5% of skeletal and 100% of non-skeletal group participants. The skeletal group was more likely to have dental signs/symptoms (prevalence ratio 1.4), early loss of primary teeth (1.7), other dental signs/symptoms (1.5), abnormal gait (2.9), any neurologic signs/symptoms (4.4), seizures (2.6), and use of mobility aids (3.7) at baseline. Results of the 6-Minute Walk Test and self-reported pain (BPI-SF), disability (HAQ-DI), and health-related quality of life (SF-36v2) scores were similar between the two groups. Disease-causing genetic variants were reported in 94.5% (skeletal group) and 93.6% (non-skeletal group) of participants. CONCLUSION: HPP is associated with substantial disease burden, including reduced mobility and quality of life, even in the absence of skeletal manifestations. These findings highlight the importance of considering HPP in patients with low ALP activity, an ALPL variant, and muscular/pain manifestations.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics