ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017
Mutational and biochemical findings in adults with persistent hypophosphatasemia.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Hypophosphatasia and Type 1 Diabetes: A Pilot Study and Review of Literature.Current osteoporosis reports · 2025Review
- Evaluation of Low Alkaline Phosphatase Levels in Clinical Practice: Implications for Diagnosing Hypophosphatasia.Calcified tissue international · 2025Article
- Article
- Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital.Journal of clinical medicine · 2024Article
- The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Musculoskeletal pain and muscular weakness as the main symptoms of adult hypophosphatasia in a Spanish cohort: clinical characterization and identification of a new ALPL gene variant.Journal of bone and mineral metabolism · 2023Article
- Dental manifestations in adult hypophosphatasia and their correlation with biomarkers.JIMD reports · 2022Article
- Pain and health-related quality of life in patients with hypophosphatasemia with and without ALPL gene mutations.Frontiers in endocrinology · 2022Article
- Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia.Journal of endocrinological investigation · 2022Article
- Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark.Bone reports · 2021Article
- Hypophosphatasia.Journal of clinical medicine · 2021Review
- Active search of adult patients with persistently low serum alkaline phosphatase levels for the diagnosis of hypophosphatasia.Archives of endocrinology and metabolism · 2021Article
- Predictive modeling of hypophosphatasia based on a case series of adult patients with persistent hypophosphatasemia.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Article
- Hypophosphatasia: is it an underdiagnosed disease even by expert physicians?Journal of bone and mineral metabolism · 2021Article
- A novel de novo heterozygous ALPL nonsense mutation associated with adult hypophosphatasia.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Article
- Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Review
- Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?Orphanet journal of rare diseases · 2020Article
- Atypical Tibial Fracture in a 63-Year-Old Woman With Intermittent Use of Bisphosphonate Unmasking Hypophosphatasia.Journal of the Endocrine Society · 2019Article
- ALPL mutations in adults with rheumatologic disorders and low serum alkaline phosphatase activity.Journal of bone and mineral metabolism · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
A majority of adults with persistently low serum alkaline phosphatase values carry a pathogenic or likely pathogenic variant in the ALPL gene and also have elevated alkaline phosphatase substrate values in serum and urine. These adults may fall within the spectrum of the adult form of hypophosphatasia.
introductionThe primary objective of this study was to determine what proportion of adults with persistently low serum alkaline phosphatase values (hypophosphatasemia) harbor mutations in the ALPL gene or have elevated alkaline phosphatase (ALP) substrates. Some adults with persistent hypophosphatasemia share clinical and radiographic features with the adult form of hypophosphatasia (HPP). In HPP, ALPL mutations result in persistent hypophosphatasemia and ALP substrate accumulation in plasma (pyridoxal-5-phosphate (PLP)) and urine (phosphoethanolamine (PEA)).
methodsBiochemical analyses, including serum ALP activity, bone-specific ALP, plasma PLP, and urine PEA, were performed in adults with persistent hypophosphatasemia. Mutational analyses were performed using PCR and Sanger sequencing methods. Gene variants were classified as pathogenic (P), likely pathogenic (LP), variants of uncertain significance (VUS), likely benign (LB), and benign (B). P and LP variants were further grouped as "Positive ALPL variants" and LB and B grouped as "Negative ALPL variants."
resultsFifty subjects completed all mutational and biochemical analyses. Sixteen percent carried only Negative ALPL variants. Of the remaining 42 subjects, 67% were heterozygous for a P variant, 19% for an LP variant, and 14% for a VUS. Biochemical results were highly inter-correlated and consistent with the expected inverse relationship between ALP and its substrates. Subjects harboring Positive ALPL variants showed lower ALP and BSAP and higher PLP and PEA values compared with subjects harboring only Negative ALPL variants. Approximately half of all subjects harboring Positive ALPL variants or ALPL VUS showed elevations in plasma PLP, and three quarters showed elevations in urine PEA.
conclusionAdults with persistent hypophosphatasemia frequently harbor ALPL mutations and have elevated ALP substrates. These adults may fall within the spectrum of the adult form of hypophosphatasia. Clinicians should take note of persistent hypophosphatasemia in their patients and be cautious in prescribing bisphosphonates when present.
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