ArticleCalcified tissue international2021
Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.
Article in Calcified tissue international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review.Journal of inherited metabolic disease · 2025Pooled it
- Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Impact of clinical symptoms on quality of life in adult hypophosphatasia: a monocentric study in northern Germany.JBMR plus · 2026Article
- Intrafamilial phenotypic variability in hypophosphatasia: evidence from two families and the literature.Frontiers in endocrinology · 2026Review
- Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025Review
- Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval.Advances in therapy · 2025Review
- Review
- The Benefits of Whole-Exome Sequencing in the Differential Diagnosis of Hypophosphatasia.International journal of molecular sciences · 2024Article
- Catalyzing precision: unraveling the diagnostic conundrum of tunisian familial hypophosphatasia case through integrative clinical and molecular approaches.Molecular genetics and genomics : MGG · 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
- Integrated multi-omics and artificial intelligence to explore new neutrophils clusters and potential biomarkers in sepsis with experimental validation.Frontiers in immunology · 2024Article
- Article
- Effects of Infantile Hypophosphatasia on Human Dental Tissue.Calcified tissue international · 2023Article
- Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia.Frontiers in endocrinology · 2023Article
- Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
- Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Review
- Anabolic actions of parathyroid hormone in a hypophosphatasia mouse model.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
- Young woman with hypophosphatasia: A case report.Clinical case reports · 2022Article
- Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?Frontiers in dental medicine · 2022Article
- Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia.Journal of endocrinological investigation · 2022Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a decreased activity of tissue nonspecific alkaline phosphatase (TNSALP). As the onset and severity of HPP are heterogenous, it can be challenging to determine the pathogenicity of detected rare ALPL variants in symptomatic patients. We aimed to characterize patients with rare ALPL variants to propose which patients can be diagnosed with adult HPP. We included 72 patients with (1) clinical symptoms of adult HPP or positive family history and (2) low TNSALP activity and/or high pyridoxal 5'-phosphate (PLP) levels, who underwent ALPL gene sequencing. The patients were analyzed and divided into three groups depending on ALPL variant pathogenicity according to the classification of the American College of Medical Genetics and Genomics (ACMG). Reported pathogenic (n = 34 patients), rare (n = 17) and common (n = 21) ALPL variants only were found. Muscular complaints were the most frequent symptoms (> 80%), followed by bone affection (> 50%). Tooth involvement was significantly more common in patients with pathogenic or rare ALPL variants. Seven rare variants could be classified as likely pathogenic (ACMG class 4) of which five have not yet been described. Inconclusive genetic findings and less specific symptoms make diagnosis difficult in cases where adult HPP is not obvious. As not every pathogenic or rare ALPL variant leads to a manifestation of HPP, only patients with bone complications and at least one additional complication concerning teeth, muscle, central nervous and mental system, repeated low TNSALP activity and high PLP levels should be diagnosed as adult HPP if rare ALPL gene variants of ACMG class 4 or higher support the diagnosis.
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