{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T14:54:35Z","timestamp":1781794475973,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rhizomelic chondrodysplasia punctata (RCDP) is a heterogenous group of disorders due to defects in genes encoding peroxisomal proteins required for plasmalogen (PL) biosynthesis, specifically PEX7 and PEX5 receptors, or GNPAT, AGPS and FAR1 enzymes. Most patients have congenital cataract and skeletal dysplasia. In the classic form, there is profound growth restriction and psychomotor delays, with most patients not advancing past infantile developmental milestones. Disease severity correlates to erythrocyte PL levels, which are almost undetectable in severe (classic) RCDP. In milder (nonclassic) forms, residual PL levels are associated with improved growth and development. However, the clinical course of this milder group remains largely unknown as only a few cases were reported. Using as inclusion criteria the ability to communicate and walk, we identified 16 individuals from five countries, ages 5\u201037\u2009years, and describe their clinical, biochemical and molecular profiles. The average age at diagnosis was 2.6\u2009years and most had cataract, growth deficiency, joint contractures, and developmental delays. Other major symptoms were learning disability (87%), behavioral issues (56%), seizures (43%), and cardiac defects (31%). All patients had decreased C16:0 PL levels that were higher than in classic RCDP, and up to 43% of average controls. Plasma phytanic acid levels were elevated in most patients. There were several common, and four novel, <jats:italic>PEX7<\/jats:italic>, and <jats:italic>GNPAT<\/jats:italic> hypomorphic alleles in this cohort. These results can be used to support earlier diagnosis and improve management in patients with mild RCDP.<\/jats:p>","DOI":"10.1002\/jimd.12349","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T19:09:15Z","timestamp":1608318555000},"page":"1021-1038","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata"],"prefix":"10.1002","volume":"44","author":[{"given":"Wedad","family":"Fallatah","sequence":"first","affiliation":[{"name":"Department of Human Genetics McGill University, Research Institute of the McGill University Health Centre  Montreal Qu\u00e9bec Canada"},{"name":"Department of Medical Genetics King Abdul\u2010Aziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Schouten","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC \u2013 location AMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Yergeau","sequence":"additional","affiliation":[{"name":"Child Health and Human Development Program Research Institute of the McGill University Health Centre  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erminia","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Child Health and Human Development Program Research Institute of the McGill University Health Centre  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC \u2013 location AMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans R.","family":"Waterham","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Amsterdam UMC \u2013 location AMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bwee Tien","family":"Poll\u2010The","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC \u2013 location AMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1621-5164","authenticated-orcid":false,"given":"Nancy","family":"Braverman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Pediatrics, Child Health and Human Development Program McGill University, Research Institute of the McGill University Health Centre  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"GeneReviews\u00ae","author":"Braverman N","year":"2001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.05.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P081620"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2003.12.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-369"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-377"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02435984"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00711817"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.10.003"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv305"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31960-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000255960.01644.39"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10124"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/346093"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01811703"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02435981"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960315)62:2<164::AID-AJMG9>3.0.CO;2-W"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-174"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/338998"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000205594.34647.d0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(95)70250-4"},{"key":"e_1_2_9_25_1","first-page":"6","article-title":"Investigational methods for peroxisomal disorders","volume":"17","author":"Steinberg S","year":"2008","journal-title":"Curr Protoc Hum Genet"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107713"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21623"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27591"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.11.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37961"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/1066527041410418"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.5.1185"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00735395"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61413"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12349","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T15:50:15Z","timestamp":1692978615000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/jimd.12349"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12349","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]},"assertion":[{"value":"2020-10-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}