{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:38Z","timestamp":1753869458951,"version":"3.41.2"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Holocarboxylase synthetase (HLCS) is a rare autosomal recessive disorder of biotin metabolism. The mutation spectrum is known to correlate with clinical phenotypes and responsiveness to biotin therapy. Five patients diagnosed with HLCS deficiency between 2015 and 2024 were recruited. Their medical records were retrospectively analyzed for clinical, laboratory, and molecular data. The diagnosis was confirmed through urine organic acid analysis, acylcarnitine profiling of blood spots, and next\u2010generation sequencing (NGS). All patients had skin rashes, either preceding metabolic decompensation or during follow\u2010up. Four patients presented in a decompensated state with respiratory distress (100%, 4\/4), seizures (50%, 2\/4), metabolic acidosis (100%, 4\/4), and encephalopathy (100%, 4\/4). Most patients (4\/5) had late\u2010onset presentations and responded well to biotin. One patient died before treatment could be given. Of the four who survived, biotin doses of 10\u201330\u2009mg daily maintained metabolic stability. The oldest patient, now 30\u2009years old, was able to have two successful pregnancies with biotin dose adjustments. Molecular analysis identified 4 mutations: of these, c.1522C&gt;T (p.Arg508Trp) is a known recurrent biotin\u2010responsive mutation, accounting for 50% of mutant alleles. The c.271del variant had not been previously reported in the literature. This is the first report of HLCS deficiency in a Malaysian population, highlighting the c.1522C&gt;T (p.Arg508Trp) variant as a target for rapid molecular screening. Most patients in this cohort have good outcomes from biotin supplementation, emphasizing the need for early intervention to prevent irreversible neurological damage.<\/jats:p>","DOI":"10.1002\/jmd2.70006","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T05:08:28Z","timestamp":1741756108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Holocarboxylase Synthetase Deficiency: Clinical, Biochemical and Molecular Findings in Five Malaysian Patients Including a Newborn Presenting as Collodion Baby"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6408-9699","authenticated-orcid":false,"given":"Siew Li","family":"Ting","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Hospital Kuala Lumpur, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusnita","family":"Yakob","sequence":"additional","affiliation":[{"name":"Unit of Molecular Diagnostics Specialised Diagnostics Centre, National Institutes of Health, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huzaimah Abdullah","family":"Sani","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Pathology Hospital Tunku Azizah, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavitha","family":"Rethanavelu","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Hospital Kuala Lumpur, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lock Hock","family":"Ngu","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Hospital Kuala Lumpur, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20204"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10532"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100603"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199912000\u201000004"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_367"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02656-y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.03.007"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199705000\u201000011"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799165"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(95)00082-8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","unstructured":"Y.Suzuki Y.AokP Y.Ishida et\u00a0al. \u201cIsolation and Characterization of Mutations in the Human Holocarboxylase Synthetase eDNA \u201d(1994) http:\/\/www.nature.com\/naturegenetics.","DOI":"10.1038\/ng1094-122"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(03)00091-X"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(02)00432-0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0020-711X(88)90202-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2019.100548"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0008-6"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.116.238956"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/127.5.710"},{"issue":"1","key":"e_1_2_12_20_1","first-page":"14","article-title":"Marginal Biotin Deficiency Is Teratogenic","volume":"223","author":"Zempleni J.","year":"2000","journal-title":"Proceedings of the Society for Experimental Biology and Medicine"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2022.100923"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2009.01357.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(82)80697-5"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2954"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.70002"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14586"},{"key":"e_1_2_12_27_1","first-page":"326","article-title":"Heterogeneity of Holocarboxylase Synthetase in Patients With Biotin\u2010Responsive Multiple Carboxylase Deficiency","volume":"37","author":"Burri B. J.","year":"1985","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.09.006"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpme.1995.23.6.477"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.03.006"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2013_252"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T21:10:33Z","timestamp":1743282633000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/jmd2.70006"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70006","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"type":"print","value":"2192-8312"},{"type":"electronic","value":"2192-8312"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70006"}}