{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:26:19Z","timestamp":1793906779445,"version":"4.8.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institute of Child Health and Human Development","award":["HD009024-01"],"award-info":[{"award-number":["HD009024-01"]}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Good Publication Practice"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Generalized arterial calcification of infancy (GACI) and autosomal recessive hypophosphatemic rickets type 2 (ARHR2) are age-related phenotypes of the rare genetic mineralization disorder, ENPP1 Deficiency, which evolve on a phenotypic continuum. To date, our understanding of the clinical spectrum of ENPP1 Deficiency is based on small studies or case reports, across which there is significant variability in clinical presentation, and limited duration of follow-up. From a previously published large retrospective natural history study, we performed a subgroup analysis to elucidate the most prevalent signs and symptoms of ENPP1 Deficiency diagnosed as GACI or ARHR2, to illustrate the onset and incidence of these complications over the lifetime, and to characterize the associated medical burden of disease. Of the 84 individuals with ENPP1 Deficiency analyzed, 51 had a recorded diagnosis of GACI, 11 were diagnosed with ARHR2, and 22 were diagnosed with both. We confirmed that those diagnosed with GACI presented predominantly with early-onset arterial calcification, respiratory distress, heart failure, and hypertension, necessitating acute inpatient care and leading to high (44%) infant mortality. Notably, we found that the majority (60.3%) of those with a history of GACI had prenatal ultrasound anomalies, including effusions, polyhydramnios, and hydrops fetalis. We estimated that 70% of individuals with ENPP1 Deficiency who survive to age 10 will have developed musculoskeletal complications, primarily rickets and\/or osteomalacia. The clinical picture of ARHR2 in this study extended beyond skeletal deformities to include hearing impairment, joint involvement, and ongoing risk of cardiovascular problems. This study sheds light on the signs and symptoms of ENPP1 Deficiency in the real world, with implications for life-long patient monitoring.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf019","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T15:45:47Z","timestamp":1738251947000},"source":"Crossref","is-referenced-by-count":7,"title":["Phenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2"],"prefix":"10.1093","volume":"9","author":[{"given":"Carlos R","family":"Ferreira","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-3165","authenticated-orcid":false,"given":"Mary 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Zulf","family":"Mughal","sequence":"additional","affiliation":[{"name":"Al Jalila Children\u2019s Specialty Hospital , Dubai ,","place":["UAE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Baujat","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre de R\u00e9f\u00e9rence Maladies Osseuses Constitutionnelles (CR MOC) et Fili\u00e8re OSCAR, H\u00f4pital Necker-Enfants Malades , 75015 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Center for Chronically Sick Children, Pediatric Endocrinology, Charit\u00e8, University Medicine Berlin , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I Manjula","family":"Schou","sequence":"additional","affiliation":[{"name":"Pulse Economics Pty Ltd. , Macquarie Park, NSW 2113 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gus","family":"Khursigara","sequence":"additional","affiliation":[{"name":"Inozyme Pharma, Inc. , Boston, MA 02210 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oona","family":"Reardon","sequence":"additional","affiliation":[{"name":"Pulse Economics Pty Ltd. , Macquarie Park, NSW 2113 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Burklow","sequence":"additional","affiliation":[{"name":"NIH Clinical Center, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Swanner","sequence":"additional","affiliation":[{"name":"Inozyme Pharma, Inc. , Boston, MA 02210 ,","place":["United 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