Disease burden by ALPL variant number in patients with non-life-threatening hypophosphatasia in the global HPP registry

Kishnani PS; Seefried L; Dahir KM; Martos-Moreno GA; Hogler W; Greenberg CR; Fang S; Petryk A; Mowrey WR; Linglart A; &Ozono K

doi:10.1530/ey.22.5.4

5.4

Prev Next

Section Contents Cite

ESPE Yearbook of Paediatric Endocrinology (2025) 22 5.4 | DOI: 10.1530/ey.22.5.4

ESPEYB25 5. Bone, Growth Plate and Mineral Metabolism Advances in Clinical Practice (6 abstracts)

5.4. Disease burden by ALPL variant number in patients with non-life-threatening hypophosphatasia in the global HPP registry

Kishnani PS , Seefried L , Dahir KM , Martos-Moreno GÁ , Högler W , Greenberg CR , Fang S , Petryk A , Mowrey WR , Linglart A &

Journal of Medical Genetics, 2025. 62(4), 249-257. https://doi.org/10.1136/jmg-2024-110383

Brief Summary: This study compared the disease burden in patients with non-life-threatening hypophosphatasia (HPP), based on the number of ALPL variants present (one versus two or more). Although patients with 2 or more variants had a higher prevalence of HPP-specific manifestations, their overall patient-reported outcomes for pain, disability and quality of life were similar to those of patients with 1 variant.

Commentary: Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterised by deficient tissue-non-specific alkaline phosphatase (ALP) enzyme activity. This leads to a wide spectrum of clinical manifestations. Although severe, life-threatening forms of HPP that manifest in infancy are well characterised, less is known about the disease burden in patients who develop symptoms after six months of age and who have varying numbers of ALPL gene variants. This study analysed data from the Global HPP Registry, focusing on patients with non-life-threatening HPP, in order to understand the relationship between the number of ALPL variants and disease burden.

The findings reveal that the disease burden associated with HPP remains high regardless of the number of ALPL variants, significantly impacting quality of life, pain, and disability across all patient groups. Patients with 2 or more ALPL variants are often diagnosed at a younger age and show a higher prevalence of specific skeletal, dental, muscular and neurological manifestations. However, there was no difference in patient-reported outcomes, such as pain and quality of life, between those with 1 variant and those with 2 or more variants. These results suggest that the clinical status of patients should be the primary consideration for access to effective treatments such as enzyme replacement therapy, rather than the number of ALPL variants alone.