{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:02:33Z","timestamp":1790809353239,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002386","name":"Cairo University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002386","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acid ceramidase deficiency is an orphan lysosomal disorder caused by\n                    <jats:italic>ASAH1<\/jats:italic>\n                    pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA\u2010PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26\u2010Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in\n                    <jats:italic>ASAH1<\/jats:italic>\n                    (12 Farber and 3 SMA\u2010PME). Recruited children were nine females\/six males ranging in age at diagnosis from 13 to 118 months. We detected\n                    <jats:italic>ASAH1<\/jats:italic>\n                    pathogenic variants in all 30 alleles including three novel variants (c.1126A&gt;G (p.Thr376Ala), c.1205G&gt;A (p.Arg402Gln), exon\u20105\u2010deletion). Both total C26\u2010Ceramide and its trans\u2010 isomer showed 100% sensitivity for the detection of\n                    <jats:italic>ASAH1<\/jats:italic>\n                    \u2010related disorders in tested patients. A 10\u2010year\u2010old girl with the novel variant c.1205G&gt;A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of\n                    <jats:italic>ASAH1<\/jats:italic>\n                    \u2010related disorders and validated the biomarker C26\u2010Ceramide for supporting diagnosis in symptomatic patients.\n                  <\/jats:p>","DOI":"10.1111\/cge.13834","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T01:14:21Z","timestamp":1598577261000},"page":"598-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>\n                      <i>ASAH1<\/i>\n                    <\/scp>\n                    \u2010related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype"],"prefix":"10.1111","volume":"98","author":[{"given":"Iman G.","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3154-1948","authenticated-orcid":false,"given":"Mohamed A.","family":"Elmonem","sequence":"additional","affiliation":[{"name":"Clinical and Chemical Pathology Department, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Division National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areef","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal M.","family":"Al\u2010Menabawy","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"El\u2010Gamal","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lobna","family":"Mansour","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Y.","family":"Issa","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Division National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-0147","authenticated-orcid":false,"given":"Mohamed S.","family":"Abdel\u2010Hamid","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics, Human Genetics and Genome Research Division National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan","family":"Abdel\u2010Hady","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Pediatrics Department Helwan University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pediatrics Department Suez Canal University  Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Solyom","sequence":"additional","affiliation":[{"name":"Enzyvant  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Albrecht\u2010Kossel\u2010Institute for Neurodegeneration, Rostock University Medical\u2010Centre and Centogene AG  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Selim","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Neurology and Metabolic division, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0845-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121573"},{"issue":"6","key":"e_1_2_8_4_1","first-page":"816","article-title":"Lipogranulomatosis; a new lipo\u2010glycoprotein storage disease","volume":"24","author":"Farber S","year":"1957","journal-title":"J Mt Sinai Hosp NY"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.51.33110"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39659"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06604-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12316"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmhg.2011.07.001"},{"key":"e_1_2_8_13_1","volume-title":"The Metabolic Basis of Inherited Disease","author":"Moser HW","year":"1989"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1358-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.28"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0250-z"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13834","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13834","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T09:00:20Z","timestamp":1693558820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,2]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/cge.13834"],"URL":"https:\/\/doi.org\/10.1111\/cge.13834","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13834\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13834\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13834\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13834\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13834\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13834\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,2]]},"assertion":[{"value":"2020-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}