Identification of hypophosphatasia in adults with persistent hypophosphatasemia: clinical-genetic characterization and a validated diagnostic tool

Mornet E (2017) Genetics of hypophosphatasia. Arch Pediatr 24(5, Supplement 2):5S51–5S6

Article  CAS  PubMed  Google Scholar 

Mornet E (2018) Hypophosphatasia. Metabolism 82:142–155

Article  CAS  PubMed  Google Scholar 

Weiss MJ, Cole DE, Ray K et al (1988) A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. Proc Natl Acad Sci U S A 85(20):7666–7669

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farman MR, Rehder C, Malli T et al (2024) The Global ALPL gene variant classification project: dedicated to deciphering variants. Bone 178:116947

Article  CAS  PubMed  Google Scholar 

Xu L, Pang Q, Jiang Y et al (2018) Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia. Biosci Rep 29;38(4):BSR20171377

Article  PubMed  PubMed Central  Google Scholar 

Zhang Q, Qin Z, Yi S et al (2021) Case report: Variations in the ALPL gene in Chinese patients with hypophosphatasia. Front Genet 12:732621

Article  PubMed  PubMed Central  Google Scholar 

Liu M, Liu M, Liang X et al (2021) Clinical and genetic characteristics of hypophosphatasia in Chinese children. Orphanet J Rare Dis 16(1):159

Article  PubMed  PubMed Central  Google Scholar 

Li X, Ren N, Wang Z et al (2023) Clinical and genetic characteristics of hypophosphatasia in Chinese adults. Genes 14(4):922

Article  PubMed  PubMed Central  Google Scholar 

Whyte MP (2016) Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 12(4):233–246

Article  CAS  PubMed  Google Scholar 

Ng E, Ashkar C, Seeman E et al (2023) A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients. Osteoporos Int 34(2):327–337

Article  CAS  PubMed  Google Scholar 

Szabo SM, Tomazos IC, Petryk A et al (2019) Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review. Orphanet J Rare Dis 14(1):85

Article  PubMed  PubMed Central  Google Scholar 

Whyte MP (2009) Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res 24(6):1132–1134

Article  PubMed  Google Scholar 

Sutton RAL, Mumm S, Coburn SP et al (2012) “Atypical femoral fractures” during bisphosphonate exposure in adult hypophosphatasia. J Bone Miner Res 27(5):987–994

Article  CAS  PubMed  Google Scholar 

Cundy T, Michigami T, Tachikawa K et al (2015) Reversible deterioration in hypophosphatasia caused by renal failure with bisphosphonate treatment. J Bone Miner Res 30(9):1726–1737

Article  CAS  PubMed  Google Scholar 

Zhou W, van Rooij JG, van de Laarschot DM et al (2023) Prevalence of monogenic bone disorders in a Dutch cohort of atypical femur fracture patients. J Bone Miner Res 38(6):896–906

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tornero C, Navarro-Compán V, Tenorio JA et al (2020) Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia? Orphanet J Rare Dis 15(1):51

Article  CAS  PubMed  PubMed Central  Google Scholar 

Garcia-Carretero R, Olid-Velilla M, Perez-Torrella D et al (2021) Predictive modeling of hypophosphatasia based on a case series of adult patients with persistent hypophosphatasemia. Osteoporos Int 32(9):1815–1824

Article  CAS  PubMed  Google Scholar 

Tornero C, Navarro-Compán V, Buño A et al (2022) Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia. Orphanet J Rare Dis 17(1):98

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sadhukhan S, Mehta P, Rajender S et al (2022) Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations. Osteoporos Int 33(12):2479–2493

Article  CAS  PubMed  Google Scholar 

Bertoldo F, Tripepi G, Zaninotto M et al (2024) Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia. J Bone Miner Res 40(1):79–86

Article  PubMed  PubMed Central  Google Scholar 

Khan AA, Brandi ML, Rush ET et al (2024) Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults. Osteoporos Int 35(3):431–438

Article  CAS  PubMed  Google Scholar 

Tornero C, Navarro-Compán V, Heath KE et al (2026) External validation of the proposed diagnostic criteria for hypophosphatasia in adults of a Spanish cohort. Osteoporos Int. Preprint at https://doi.org/10.1007/s00198-026-07881-2

Dahir KM, Below JE, Liu J et al (2025) Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository. J Bone Miner Res 41(3):270–281

Article  Google Scholar 

Bland JM, Altman DG (2000) The odds ratio. BMJ 320(7247):1468

Article  CAS  PubMed  PubMed Central  Google Scholar 

Riancho-Zarrabeitia L, García-Unzueta M, Tenorio JA et al (2016) Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults. Eur J Intern Med 29:40–45

Article  CAS  PubMed  Google Scholar 

Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424

Article  PubMed  PubMed Central  Google Scholar 

Critchlow AJ, Alexander SE, Hiam DS et al (2025) Associations between female sex hormones and skeletal muscle ageing: the Baltimore Longitudinal Study of Aging. J Cachexia Sarcopenia Muscle 16(3):e13786

Article  PubMed  PubMed Central  Google Scholar 

Li H, Wang H (2025) Association between weekend warrior physical activity pattern and bone mineral density among adults: national health and nutrition examination survey. Osteoporos Int 36(7):1221–1229

Article  PubMed  PubMed Central  Google Scholar 

Le Du MH, Stigbrand T, Taussig MJ et al (2001) Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity. J Biol Chem 276(12):9158–65

Silvent J, Gasse B, Mornet E et al (2014) Molecular evolution of the tissue-nonspecific alkaline phosphatase allows prediction and validation of missense mutations responsible for hypophosphatasia. J Biol Chem 289(35):24168–24179

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu Y, Rong K, Yao D et al (2023) The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase. Nat Commun 14(1):4048

Article  CAS  PubMed  PubMed Central  Google Scholar 

Högler W, Langman C, Gomes da Silva H et al (2019) Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskelet Disord 20(1):80

Article  PubMed  PubMed Central  Google Scholar 

Genest F, Seefried L (2018) Subtrochanteric and diaphyseal femoral fractures in hypophosphatasia-not atypical at all. Osteoporos Int 29(

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