Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository
An erratum to this article was published (J Bone Miner Res, 11 Oct 2026 ↗)
Authors' conclusion
Overall, the data support our hypothesis and aids the management of carriers of pathogenic ALPL variants.
Study context
- Population
- Unselected individuals visiting a tertiary care, academic medical center, with genome sequencing
- Participants
- 37,147 genomes
- Exposure
- Carriers of pathogenic or likely-pathogenic ALPL variants (ALPL+) vs controls lacking such variants (ALPL-)
- ALPL+n = 70
- ALPL-n = 148reference
- Outcome
- Prevalence of pathogenic or likely-pathogenic ALPL variants and HPP penetrance in adult carriers
Methodological detailsunselected biorepository, single tertiary care academic medical center
- Unselected biorepository
- Single tertiary care academic medical center
Main finding
As reported in the abstract
- Prevalence of pathogenic or likely-pathogenic ALPL variants
- 0.3% (n = 109) or 1/341
- Most frequent variant c.571G>A
- 67.9%
- ALPL+ with mild, mainly neurological, symptoms often reported in adults with hypophosphatasia (HPP)
- 70/70
- ALPL+ with low serum alkaline phosphatase (ALP)
- 65.7% (38/70)
- ALPL+ meeting consensus diagnostic criteria for HPP
- 12.9% (9/70)
Observational data: associations, not effects.
Further findings
Progression of mobility issues · higher probability of progression with ALPL+ · median age
P = 0.03
- ALPL- meeting diagnostic criteria for HPP
- 3.4% · 5 of 148
- ALPL- meeting diagnostic criteria for HPP: 5/148
Progression of fatigue, arthritis or dental problems
- Similar probability of progression in ALPL+ vs ALPL-
Original publication
Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository. J Bone Miner Res. Published 21 November 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →