{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:30:04Z","timestamp":1771057804131,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Acid-labile subunit (ALS) deficiency (ACLSD), caused by homozygous or compound heterozygous <jats:italic>IGFALS<\/jats:italic> mutations, is associated with moderate short stature, delayed puberty, low serum IGF-I and ALS and extremely low serum IGFBP-3. Its effect on birth weight, head circumference, bone mineral density (BMD), serum IGF-II and IGFBP-2 is uncertain, as well as the phenotype of heterozygous carriers of <jats:italic>IGFALS<\/jats:italic> mutations (partial ACLSD).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>From all available members of five Turkish families, carrying three mutations in exon 2 of <jats:italic>IGFALS<\/jats:italic> (c.1462G\u2009&gt;\u2009A, p.Asp488Asn (families A, B, E); c.251A\u2009&gt;\u2009G, p.Asn84Ser (families C and E) and c.1477del, p.Arg493fs (family D)), clinical, laboratory and BMD data were collected.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Auxological and biochemical findings were expressed as SDS for age and gender. Ternary complex formation in serum was investigated by size-exclusion chromatography. BMD using DXA bone densitometry was adjusted for height and age (Ha-BMD z-score).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In ACLSD (<jats:italic>n<\/jats:italic>\u2009=\u200924), mean\u2009\u00b1\u2009<jats:sc>s.d.<\/jats:sc> height SDS (\u22122.7\u2009\u00b1\u20091.2), head circumference SDS (\u22122.3\u2009\u00b1\u20090.5) and body mass index (BMI) (\u22120.6\u2009\u00b1\u20091.0 SDS) were lower than those in partial ACLSD (<jats:italic>n<\/jats:italic>\u2009=\u200926, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.01) and birth weight SDS (<jats:italic>n<\/jats:italic>\u2009=\u20097) tended to be lower (\u22122.2\u2009\u00b1\u20091.1 vs \u22120.6\u2009\u00b1\u20090.3 in partial ACLSD (<jats:italic>P<\/jats:italic>\u2009=\u20090.07)). Serum IGF-I was \u22123.7\u2009\u00b1\u20091.4 vs \u22121.0\u2009\u00b1\u20091.0, IGF-II: \u22125.6\u2009\u00b1\u20090.7 vs \u22121.3\u2009\u00b1\u20090.7, ALS: &lt;\u22124.4\u2009\u00b1\u20091.2 vs \u22122.1\u2009\u00b1\u20090.9 and IGFBP-3: \u22129.0\u2009\u00b1\u20091.9 vs \u22121.6\u2009\u00b1\u20090.8 SDS respectively (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Ha-BMD z-score was similar and normal in both groups.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>To the known phenotype of ACLSD (i.e. short stature, reduced serum levels of IGF-I and ALS, extremely low serum IGFBP-3 and disturbed ternary complex formation), we add reduced birth weight, head circumference and serum IGF-II.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0999","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T01:40:37Z","timestamp":1488418837000},"page":"657-667","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":29,"title":["Clinical and biochemical characteristics and bone mineral density of homozygous, compound heterozygous and heterozygous carriers of three novel IGFALS mutations"],"prefix":"10.1093","volume":"176","author":[{"given":"Emreg\u00fcl","family":"I\u015f\u0131k","sequence":"first","affiliation":[{"name":"1Department of Pediatric EndocrinologyGaziantep Children\u2019s Hospital, Gaziantep, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belma","family":"Haliloglu","sequence":"additional","affiliation":[{"name":"2Department of Pediatric EndocrinologyYeditepe University School of Medicine, \u0130stanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap","family":"van Doorn","sequence":"additional","affiliation":[{"name":"3Department of GeneticsUniversity Medical Center Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00fcseyin","family":"Demirbilek","sequence":"additional","affiliation":[{"name":"4Department of Pediatric EndocrinologyHacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sitha A","family":"Scheltinga","sequence":"additional","affiliation":[{"name":"5Departments of Clinical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Losekoot","sequence":"additional","affiliation":[{"name":"5Departments of Clinical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M","family":"Wit","sequence":"additional","affiliation":[{"name":"6Departments of PediatricsLeiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"2017041317200932000_176.6.657.1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1700063"},{"key":"2017041317200932000_176.6.657.2","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJMoa013100","article-title":"Deficiency of the circulating insulin-like growth factor system associated with inactivation of the acid-labile subunit gene","volume":"350","author":"Domene","year":"2004","journal-title":"New Engeland Journal of Medicine"},{"key":"2017041317200932000_176.6.657.3","doi-asserted-by":"publisher","DOI":"10.1159\/000232486"},{"key":"2017041317200932000_176.6.657.4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.beem.2010.08.010","article-title":"Acid-labile subunit (ALS) deficiency","volume":"25","author":"Domene","year":"2011","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"2017041317200932000_176.6.657.5","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.1210753"},{"key":"2017041317200932000_176.6.657.6","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/cen.12200","article-title":"A novel mutation in IGFALS, c.380T>C (p.L127P), associated with short stature, delayed puberty, osteopenia and hyperinsulinaemia in two siblings: insights into the roles of insulin growth factor-1 (IGF1).","volume":"79","author":"Hess","year":"2013","journal-title":"Clinical Endocrinology"},{"key":"2017041317200932000_176.6.657.7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1159\/000355927","article-title":"Novel acid-labile subunit (IGFALS) mutation p.T145K (c.434C>A) in a patient with ALS deficiency, normal stature and immunological dysfunction","volume":"80","author":"Schreiner","year":"2013","journal-title":"Hormone Research in Paediatrics"},{"key":"2017041317200932000_176.6.657.8","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1159\/000358329","article-title":"A novel homozygous mutation of the IGFALS gene in a female adolescent: indirect evidence for a contributing role of the circulating IGF-I pool in the pubertal growth spurt","volume":"81","author":"Poukoulidou","year":"2014","journal-title":"Hormone Research in Paediatrics"},{"key":"2017041317200932000_176.6.657.9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3718"},{"key":"2017041317200932000_176.6.657.10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1152"},{"key":"2017041317200932000_176.6.657.11","doi-asserted-by":"publisher","DOI":"10.1159\/000183899"},{"key":"2017041317200932000_176.6.657.12","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0081"},{"key":"2017041317200932000_176.6.657.13","doi-asserted-by":"publisher","DOI":"10.1159\/000098479"},{"key":"2017041317200932000_176.6.657.14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2678"},{"key":"2017041317200932000_176.6.657.15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s40618-014-0195-1","article-title":"Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency","volume":"38","author":"Storr","year":"2015","journal-title":"Journal of Endocrinological Investigation"},{"key":"2017041317200932000_176.6.657.16","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0541"},{"key":"2017041317200932000_176.6.657.17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2842"},{"key":"2017041317200932000_176.6.657.18","first-page":"43","article-title":"Acid-labile subunit deficiency: phenotypic similarities and differences between human and mouse","volume":"28","author":"Domene","year":"2005","journal-title":"Journal of Endocrinological Investigation"},{"key":"2017041317200932000_176.6.657.19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0489"},{"key":"2017041317200932000_176.6.657.20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1159\/000355412","article-title":"Heterozygous IGFALS gene variants in idiopathic short stature and normal children: impact on height and the IGF system","volume":"80","author":"Domene","year":"2013","journal-title":"Hormone Research in Paediatrics"},{"key":"2017041317200932000_176.6.657.21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000355017","article-title":"Clinical features of a new acid-labile subunit (IGFALS) heterozygous mutation: anthropometric and biochemical characterization and response to growth hormone administration","volume":"81","author":"Grandone","year":"2014","journal-title":"Hormone Research in Paediatrics"},{"key":"2017041317200932000_176.6.657.22","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4274\/jcrpe.2183","article-title":"Reference values for weight, height, head circumference, and body mass index in turkish children","volume":"7","author":"Neyzi","year":"2015","journal-title":"Journal of Clinical Research in Pediatric Endocrinology"},{"key":"2017041317200932000_176.6.657.23","doi-asserted-by":"publisher","DOI":"10.1136\/adc.45.244.755"},{"key":"2017041317200932000_176.6.657.24","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200003000-00006"},{"key":"2017041317200932000_176.6.657.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1991.tb11945.x"},{"key":"2017041317200932000_176.6.657.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2009.09.008"},{"key":"2017041317200932000_176.6.657.27","doi-asserted-by":"crossref","unstructured":"Greulich WW Pyle SJ. Radiographic Atlas of Skeletal Development of the Hand and Wrist. California, USA: Stanford University Press, 1959.","DOI":"10.1097\/00000441-195909000-00030"},{"key":"2017041317200932000_176.6.657.28","doi-asserted-by":"publisher","DOI":"10.1159\/000023268"},{"key":"2017041317200932000_176.6.657.29","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1508"},{"key":"2017041317200932000_176.6.657.30","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1210\/jc.2015-1410","article-title":"levels, complex formation, and igf bioactivity in growth hormone-treated children with prader-willi syndrome","volume":"100","author":"Bakker","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2017041317200932000_176.6.657.31","doi-asserted-by":"crossref","first-page":"E1988","DOI":"10.1210\/jc.2013-3814","article-title":"Ternary complex formation and IGFBP-3 proteolytic activity during childhood: age-dependent changes","volume":"99","author":"Renes","year":"2014","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2017041317200932000_176.6.657.32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007038"},{"key":"2017041317200932000_176.6.657.33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1111"},{"key":"2017041317200932000_176.6.657.34","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1159\/000355543","article-title":"A database and website for molecular defects of the GH-IGF axis: www.growthgenetics.com.","volume":"80","author":"Rosenfeld","year":"2013","journal-title":"Hormone Research in Paediatrics"},{"key":"2017041317200932000_176.6.657.35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1210\/me.2010-0295","article-title":"D440N mutation in the acid-labile subunit of insulin-like growth factor complexes inhibits secretion and complex formation","volume":"25","author":"Firth","year":"2011","journal-title":"Molecular Endocrinology"},{"key":"2017041317200932000_176.6.657.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23328"},{"key":"2017041317200932000_176.6.657.37","doi-asserted-by":"publisher","DOI":"10.1530\/JME-12-0086"},{"key":"2017041317200932000_176.6.657.38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610313351805"},{"key":"2017041317200932000_176.6.657.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010107"},{"key":"2017041317200932000_176.6.657.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.07.028"},{"key":"2017041317200932000_176.6.657.41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1254"},{"key":"2017041317200932000_176.6.657.42","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1597"},{"key":"2017041317200932000_176.6.657.43","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.beem.2010.09.012","article-title":"IGF1R mutations as cause of SGA","volume":"25","author":"Klammt","year":"2011","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"2017041317200932000_176.6.657.44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.beem.2010.08.005","article-title":"IGF1 molecular anomalies demonstrate its critical role in fetal, postnatal growth and brain development","volume":"25","author":"Netchine","year":"2011","journal-title":"Best Practice and Research: Clinical Endocrinology and Metabolism"},{"key":"2017041317200932000_176.6.657.45","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1056\/NEJMoa1415227","article-title":"Paternally inherited IGF2 mutation and growth restriction","volume":"373","author":"Begemann","year":"2015","journal-title":"New England Journal of Medicine"},{"key":"2017041317200932000_176.6.657.46","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.pedneo.2013.09.002","article-title":"Association of umbilical cord plasma acid-labile subunit of the insulin-like growth factor ternary complex with anthropometry in term newborns","volume":"55","author":"Tseng","year":"2014","journal-title":"Pediatrics and Neonatology"},{"key":"2017041317200932000_176.6.657.47","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1002\/jbmr.94","article-title":"Sex-specific regulation of body size and bone slenderness by the acid labile subunit","volume":"25","author":"Courtland","year":"2010","journal-title":"Journal of Bone and Mineral Research"},{"key":"2017041317200932000_176.6.657.48","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(03)00113-5"},{"key":"2017041317200932000_176.6.657.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2007.12.005"},{"key":"2017041317200932000_176.6.657.50","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jbmr.5650070204","article-title":"New approaches for interpreting projected bone densitometry data","volume":"7","author":"Carter","year":"1992","journal-title":"Journal of Bone and Mineral Research"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/176\/6\/657.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/EJE-16-0999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:10:17Z","timestamp":1676391017000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/176\/6\/657\/6655163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":50,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-16-0999","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}