biostudies-literatureUnknown17(1)Chunn LMDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesInozyme Pharma<h4>Background</h4>ENPP1 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.<h4>Methods</h4>We 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.<h4>Results</h4>We 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.<h4>Conclusion</h4>These 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.Orphanet journal of rare diseases421https://www.ebi.ac.uk/biostudies/studies/S-EPMC9717445biostudies-literatureEstimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.PMC9717445Heinrich SVRutsch FBissonnette JKiel MJFerreira CRChunn LMMercurio SAfalseEstimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.<h4>Background</h4>ENPP1 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.<h4>Methods</h4>We 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.<h4>Results</h4>We 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.<h4>Conclusion</h4>These 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.2022-01-01T00:00:00Z2022 Dec2026-06-20T03:13:17.782Z2025-04-04T13:46:32.32ZS-EPMC97174453646101410.1186/s13023-022-02577-2