{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:09:36Z","timestamp":1774645776901,"version":"3.50.1"},"reference-count":38,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"j_jpem-2019-0466_s_999_w2aab3b7c35b1b6b1aab1c16b1Aa\"><jats:title>Background<\/jats:title><jats:p>Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) defects. Patients with HVDRR do not respond to standard doses of calcitriol and oral calcium (Ca) treatment and need to be treated with intravenous Ca (IV-Ca) <jats:italic>via<\/jats:italic> a central route. However, central catheter-related complications can cause significant morbidity.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2019-0466_s_998_w2aab3b7c35b1b6b1aab1c16b2Aa\"><jats:title>Case presentation<\/jats:title><jats:p>Four unrelated patients with HVDRR presenting with rickets and alopecia totalis were administered intermittent IV-Ca treatment (2\u20135 times\/week) through a peripheral route. No complications such as infection, extravasation or arrhythmias were detected upon peripheral infusion. Peripheral 1\u201322 months\u2019 duration of IV-Ca normalized parathyroid hormone (PTH) and alkaline phosphatase (ALP) in all patients, after which, oral Ca of 200\u2013400 mg\/kg\/day and calcitriol of 0.5 \u03bcg\/kg\/day were sufficient to maintain normal PTH levels. Molecular studies on the <jats:italic>VDR<\/jats:italic> gene showed a previously reported homozygous c.454C\u2009&gt;\u2009T (p.<jats:italic>Q152*<\/jats:italic>) pathogenic variant in two patients. Two novel homozygous variants in the other two patients were detected: (1) <jats:italic>c.756-2A\u2009&gt;\u2009G<\/jats:italic>, which affects the splice acceptor site, and (2) <jats:italic>c.66dupG<\/jats:italic> (p.I23Dfs*20) variant leading to a frameshift that results in a premature stop codon.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2019-0466_s_997_w2aab3b7c35b1b6b1aab1c16b3Aa\"><jats:title>Conclusions<\/jats:title><jats:p>Peripheral IV-Ca treatment is an effective and practical alternative treatment mode that provides dramatic clinical benefit in patients with HVDRR.<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2019-0466","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T09:03:16Z","timestamp":1581498196000},"page":"557-562","source":"Crossref","is-referenced-by-count":6,"title":["Hereditary vitamin D-resistant rickets: a report of four cases with two novel variants in the VDR gene and successful use of intermittent intravenous calcium via a peripheral route"],"prefix":"10.1515","volume":"33","author":[{"given":"Sayg\u0131n","family":"Abal\u0131","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"},{"name":"Department of Pediatrics, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayuko","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serap","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeynep","family":"Atay","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u0131nar","family":"Isguven","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, School of Medicine, Sakarya University, Sakarya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00fclay","family":"G\u00fcran","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belma","family":"Haliloglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serpil","family":"Ba\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Isojima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Kitanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah","family":"Bereket","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref41","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bonr.2015.05.001","article-title":"Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: a novel mechanism of dominant inheritance","volume":"2","year":"2015","journal-title":"Bone Reports"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation predicton for the deep-sequencing age","volume":"11","year":"2014","journal-title":"Nat Methods"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bonr.2015.05.001","article-title":"Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: a novel mechanism of dominant inheritance","volume":"2","year":"2015","journal-title":"Bone Reports"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels","volume":"31","year":"2015","journal-title":"Bioinformatics"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","year":"2017","journal-title":"Hum Genet"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1210\/mend-3-4-635","article-title":"Functional domains of the human vitamin D3 receptor regulate osteocalcin gene expression","volume":"3","year":"1989","journal-title":"Mol Endocrinol"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1172\/JCI112483","article-title":"Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D","volume":"77","year":"1986","journal-title":"J Clin Invest"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels","volume":"31","year":"2015","journal-title":"Bioinformatics"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1210\/mend-3-4-635","article-title":"Functional domains of the human vitamin D3 receptor regulate osteocalcin gene expression","volume":"3","year":"1989","journal-title":"Mol Endocrinol"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","year":"2019","journal-title":"Bioinformatics"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000367711","article-title":"Successful intermittent intravenous calcium treatment via the peripheral route in a patient with hereditary vitamin D-resistant rickets and alopecia","volume":"83","year":"2015","journal-title":"Horm Res Paediatr"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","year":"2010","journal-title":"Nat Methods"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s00774-009-0079-1","article-title":"Hypophosphatemia: the common denominator of all rickets","volume":"27","year":"2009","journal-title":"J Bone Miner Metab"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0002-9343(84)90516-3","article-title":"1,25-dihydroxyvitamin D resistance, rickets, and alopecia","volume":"77","year":"1984","journal-title":"Am J Med"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"e0131157","DOI":"10.1371\/journal.pone.0131157","article-title":"Detection of hereditary 1,25-hydroxyvitamin D resistant rickets caused by uniparental disomy of chromosome 12 using genome-wide single nucleotide polymorphism array","volume":"10","year":"2015","journal-title":"PLoS ONE"},{"key":"ref321","first-page":"801","article-title":"Vitamin D dependent rickets, diagnostic and therapeutic difficulties: two case reports","volume":"24","year":"2011","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0002-9343(84)90516-3","article-title":"1,25-dihydroxyvitamin D resistance, rickets, and alopecia","volume":"77","year":"1984","journal-title":"Am J Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s00774-009-0079-1","article-title":"Hypophosphatemia: the common denominator of all rickets","volume":"27","year":"2009","journal-title":"J Bone Miner Metab"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI116539","article-title":"Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3","volume":"92","year":"1993","journal-title":"J Clin Invest"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI116539","article-title":"Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3","volume":"92","year":"1993","journal-title":"J Clin Invest"},{"key":"ref211","first-page":"57","article-title":"The vitamin D hormone and its nuclear receptor: molecular actions and disease states","volume":"154","year":"1997","journal-title":"J Endocrinol"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ecl.2010.02.004","article-title":"Genetic disorders and defects in vitamin D action","volume":"39","year":"2010","journal-title":"Endocrinol Metab Clin North Am"},{"key":"ref131","first-page":"801","article-title":"Vitamin D dependent rickets, diagnostic and therapeutic difficulties: two case reports","volume":"24","year":"2011","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","year":"2017","journal-title":"Hum Genet"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0022-3476(05)81919-5","article-title":"Calcium therapy for calcitriol-resistant rickets","volume":"121","year":"1992","journal-title":"J Pediatr"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0022-3476(05)81919-5","article-title":"Calcium therapy for calcitriol-resistant rickets","volume":"121","year":"1992","journal-title":"J Pediatr"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e0131157","DOI":"10.1371\/journal.pone.0131157","article-title":"Detection of hereditary 1,25-hydroxyvitamin D resistant rickets caused by uniparental disomy of chromosome 12 using genome-wide single nucleotide polymorphism array","volume":"10","year":"2015","journal-title":"PLoS ONE"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000362618","article-title":"Identification of a novel nonsense mutation in the ligand-binding domain of the vitamin d receptor gene and clinical description of two greek patients with hereditary vitamin d-resistant rickets and alopecia","volume":"82","year":"2014","journal-title":"Horm Res Paediatr"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000367711","article-title":"Successful intermittent intravenous calcium treatment via the peripheral route in a patient with hereditary vitamin D-resistant rickets and alopecia","volume":"83","year":"2015","journal-title":"Horm Res Paediatr"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ecl.2010.02.004","article-title":"Genetic disorders and defects in vitamin D action","volume":"39","year":"2010","journal-title":"Endocrinol Metab Clin North Am"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/BF02024336","article-title":"Two siblings with vitamin-D-dependent rickets type II: no recurrence of rickets for 14 years after cessation of therapy","volume":"149","year":"1989","journal-title":"Eur J Pediatr"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","year":"2010","journal-title":"Nat Methods"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000362618","article-title":"Identification of a novel nonsense mutation in the ligand-binding domain of the vitamin d receptor gene and clinical description of two greek patients with hereditary vitamin d-resistant rickets and alopecia","volume":"82","year":"2014","journal-title":"Horm Res Paediatr"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/BF02024336","article-title":"Two siblings with vitamin-D-dependent rickets type II: no recurrence of rickets for 14 years after cessation of therapy","volume":"149","year":"1989","journal-title":"Eur J Pediatr"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","year":"2019","journal-title":"Bioinformatics"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation predicton for the deep-sequencing age","volume":"11","year":"2014","journal-title":"Nat Methods"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1172\/JCI112483","article-title":"Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D","volume":"77","year":"1986","journal-title":"J Clin Invest"},{"key":"ref21","first-page":"57","article-title":"The vitamin D hormone and its nuclear receptor: molecular actions and disease states","volume":"154","year":"1997","journal-title":"J Endocrinol"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"link":[{"URL":"https:\/\/www.degruyter.com\/view\/journals\/jpem\/33\/4\/article-p557.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2019-0466\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T01:47:01Z","timestamp":1619056021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2019-0466\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":38,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1515\/jpem-2019-0466","relation":{},"ISSN":["2191-0251","0334-018X"],"issn-type":[{"value":"2191-0251","type":"electronic"},{"value":"0334-018X","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4,28]]}}}