ReviewOrphanet journal of rare diseases2022
Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.
Review in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.Journal of endocrinological investigation · 2026Review
- Benchmarking genetic birth prevalence estimates against newborn screening data.American journal of human genetics · 2026Article
- Six cases ofJBMR plus · 2025Article
- A Fragile Phosphate/Pyrophosphate Balance: From Essential Mineralization to Rare Calcifying Diseases.Current osteoporosis reports · 2025Review
- Article
- Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.Calcified tissue international · 2025Article
- Article
- Use of Whole-Exome Sequencing and Pedigree Analysis to Identify X-linked Hypophosphatemia in Saudi Arabian Families.Journal of the Endocrine Society · 2024Article
- Homozygous splice-site variant in ENPP1 underlies generalized arterial calcification of infancy.BMC pediatrics · 2024Article
- An estimation of global genetic prevalence of PLA2G6-associated neurodegeneration.Orphanet journal of rare diseases · 2024Article
- Case report: Multiple arterial stenoses induced by autosomal-recessive hypophosphatemic rickets type 2 associated with mutation of ENPP1: a case study.Frontiers in cardiovascular medicine · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundENPP1 Deficiency-caused by biallelic variants in ENPP1-leads to widespread arterial calcification in early life (Generalized Arterial Calcification of Infancy, GACI) or hypophosphatemic rickets in later life (Autosomal Recessive Hypophosphatemic Rickets type 2, ARHR2). A prior study using the Exome Aggregation Consortium (ExAC)-a database of exomes obtained from approximately 60,000 individuals-estimated the genetic prevalence at approximately 1 in 200,000 pregnancies.
methodsWe estimated the genetic prevalence of ENPP1 Deficiency by evaluating allele frequencies from a population database, assuming Hardy-Weinberg equilibrium. This estimate benefitted from a comprehensive literature review using Mastermind ( https://mastermind.genomenon.com/ ), which uncovered additional variants and supporting evidence, a larger population database with approximately 140,000 individuals, and improved interpretation of variants as per current clinical guidelines.
resultsWe estimate a genetic prevalence of approximately 1 in 64,000 pregnancies, thus more than tripling the prior estimate. In addition, the carrier frequency of ENPP1 variants was found to be highest in East Asian populations, albeit based on a small sample.
conclusionThese results indicate that a significant number of patients with ENPP1 Deficiency remain undiagnosed. Efforts to increase disease awareness as well as expand genetic testing, particularly in non-European populations are warranted, especially now that clinical trials for enzyme replacement therapy, which proved successful in animal models, are underway.
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