SynthesisOrphanet journal of rare diseases2019
Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review.
Synthesis in Orphanet journal of rare diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Trial
- Prevalence of hypophosphatasia in general and selected patient populations: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Evolving Therapeutic Paradigms in Pediatric Hypophosphatasia: From Survival-Driven Care to Integrated Precision Management.International journal of molecular sciences · 2026Review
- Identification of hypophosphatasia in adults with persistent hypophosphatasemia: clinical-genetic characterization and a validated diagnostic tool.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Hypophosphatasia: low penetrance of pathogenic and likely-pathogenic ALPL variants identified through an unselected biorepository.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Biochemical phenotype of hypophosphatasia in asymptomatic individuals carrying ALPL variants.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Impact of clinical symptoms on quality of life in adult hypophosphatasia: a monocentric study in northern Germany.JBMR plus · 2026Article
- The Global Hypophosphatasia Registry: lessons learned from a decade of real-world data.Orphanet journal of rare diseases · 2025Review
- Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025Review
- Multigenerational genetic inheritance and clinical characteristics of the rare disease hypophosphatasia in 6 families: A case series.Bone reports · 2025Article
- Disease burden byJournal of medical genetics · 2025Article
- [Rare osteological diseases in the rheumatological consultation: hypophosphatasia and phosphate loss syndromes].Zeitschrift fur Rheumatologie · 2025Review
- A systematic literature review of the impact and measurement of mobility impairment in rare bone diseases.Therapeutic advances in musculoskeletal disease · 2025Review
- Phenotype and genotype of hypophosphatasia cases in Saudi Arabia: multi-center case cohort.Frontiers in genetics · 2025Article
- Raman Spectroscopic Analysis of Molecular Structure and Mechanical Properties of Hypophosphatasia Primary Tooth.Molecules (Basel, Switzerland) · 2024Article
- A Delphi panel to build consensus on assessing disease severity and disease progression in adult patients with hypophosphatasia in the United States.Journal of endocrinological investigation · 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
- Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Could Some Patients With Fibromyalgia Potentially Have Hypophosphatasia? A Retrospective Single-Center Study.ACR open rheumatology · 2023Article
- Reducing diagnostic delay in hypophosphatasia: a case series of 14 patients presenting to general rheumatology.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by bone mineralization defects and systemic complications. Understanding of the clinical course and burden of HPP is limited by its rarity. This systematic literature review and synthesis of case report data aimed to determine the frequency and timing of clinical HPP manifestations and events.
methodsCase reports and series of patients with HPP who had been followed longitudinally for ≥1 year were identified. Demographics and clinical data of interest, identified through consultation with clinical experts in HPP, were extracted. Occurrences of clinical manifestations/events of interest were categorized, classified by age at first reported occurrence of HPP manifestations and visualized over time. Clinical manifestations/events considered to contribute to the clinical burden of HPP were identified. Kaplan-Meier curves were used to estimate the median (range) age at first occurrence of the most frequently reported manifestations/events.
resultsFrom the 283 studies that met the inclusion criteria, 265 patients with HPP with ≥1 year of longitudinal follow-up were identified (median [interquartile range] age 4 [0-34] years; 45% male). The types of clinical manifestations/events of interest experienced by individuals with ≥1 such manifestation/event (n = 261) often differed between older and younger patients. Most (94%) of the 265 patients experienced ≥1 manifestation/event deemed to contribute to the clinical burden of HPP; premature tooth loss (53.5%), fractures (35.8%), pain (33.6%), and gross motor/ambulation difficulties (30.9%) were most frequently reported. The median (range) age at first reported occurrence of respiratory symptoms, cranial abnormalities, and premature tooth loss ranged from 0.3 to 10 years, whereas the median age at first reported occurrence of fractures, pain, gross motor/ambulation difficulties, and surgery ranged from 33 to 70 years.
conclusionsHPP is associated with a high clinical burden of disease, regardless of age at first reported occurrence of HPP manifestations. Over an individual's lifetime, the types of manifestations/events experienced can change and multiple HPP-related clinical manifestations/events can accumulate. These observations may reflect evolution and progression of the disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.