{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T23:50:21Z","timestamp":1769212221370,"version":"3.49.0"},"reference-count":23,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["FOR2509: TH1461\/7-2"],"award-info":[{"award-number":["FOR2509: TH1461\/7-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The congenital disorders of glycosylation (CDG) encompass &gt;190 multiorgan disorders with predominantly neurodevelopmental phenotypes with no causative treatment available. The glycoprotein biotinidase (BTD) provides biotin, an essential cofactor for carboxylases in ubiquitous metabolic pathways. Individuals with (partial) BTD deficiency (BTDD) and CDG patients show overlapping phenotypes like movement disorders, seizures, and neurodevelopmental issues. Biotin is a water-soluble, inexpensive, and safe food supplement. Patients with primary BTDD respond well to oral biotin supplement. We here explore secondary BTDD and the effect of biotin supplementation in PMM2-CDG in an initial open-label study.<\/jats:p>\n                  <jats:p>BTD activity in dried blood spots from 29 individuals with PMM2-CDG indicated a mean reduction to 27% (range: 23.0\u201340.5%) at group level. Patients (mean: 19.6\u2009\u00b1\u200911.9 years) were supplemented with 10\u2009mg biotin daily for 12 months. The parents\/caretaker reported positive responses in 62 to 69% of patients across seven (performance, social, at home, self-control, self-care, leisure, health) of the nine categories covered by the Adaptive Behavior Assessment System-II (ABAS-II) questionnaires. The reported positive effect of biotin supplementation differed between age groups, ranging from 54% (16\u201343 years) via 62% (2\u20135 years) to 80% (6\u201313 years). Its effect was reported to be the highest in the moderate to severely affected patient subgroups, with significant improvements in home functioning, health, performance, leisure, self-control. No adverse effects were reported.<\/jats:p>\n                  <jats:p>Given the absence of other treatments, the supportive effect of Biotin in PMM2-CDG deserves further exploration.<\/jats:p>","DOI":"10.1055\/a-2708-3016","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T22:59:47Z","timestamp":1759791587000},"page":"042-050","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Secondary Biotinidase Deficiency and Biotin Supplementation in PMM2-CDG"],"prefix":"10.1055","volume":"57","author":[{"given":"Nastassja","family":"Himmelreich","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen G.","family":"Okun","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Hengst","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Geiger","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Barone","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy"},{"name":"Research Unit of Rare Diseases and Neurodevelopmental Disorders, Oasi Research Institute-IRCCS, Troina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia B.","family":"Wortmann","sequence":"additional","affiliation":[{"name":"University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria"},{"name":"Integriertes Sozialp\u00e4diatrisches Zentrum (iSPZ), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-8747","authenticated-orcid":false,"given":"Christian","family":"Thiel","sequence":"additional","affiliation":[{"name":"Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"108476","DOI":"10.1016\/j.ymgme.2024.108476","article-title":"Clinical and biochemical footprints of congenital disorders of glycosylation: proposed nosology","volume":"142","author":"B G Ng","year":"2024","journal-title":"Mol Genet Metab"},{"issue":"11","key":"ref2","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1021\/acschembio.1c00601","article-title":"Chemical therapies for congenital disorders of glycosylation","volume":"17","author":"P Sosicka","year":"2022","journal-title":"ACS Chem Biol"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41436-019-0647-2","article-title":"Therapeutic approaches in congenital disorders of glycosylation (CDG) involving N-linked glycosylation: an update","volume":"22","author":"J Verheijen","year":"2020","journal-title":"Genet Med"},{"issue":"09","key":"ref4","doi-asserted-by":"crossref","first-page":"e14332","DOI":"10.15252\/emmm.202114332","article-title":"A spoonful of L-fucose-an efficient therapy for GFUS-CDG, a new glycosylation disorder","volume":"13","author":"R G Feichtinger","year":"2021","journal-title":"EMBO Mol Med"},{"issue":"15","key":"ref5","doi-asserted-by":"crossref","first-page":"8725","DOI":"10.3390\/ijms23158725","article-title":"Systematic review: drug repositioning for congenital disorders of glycosylation (CDG)","volume":"23","author":"S Brasil","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"04","key":"ref6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/jimd.12073","article-title":"Biotin in metabolism, gene expression, and human disease","volume":"42","author":"A Le\u00f3n-Del-R\u00edo","year":"2019","journal-title":"J Inherit Metab Dis"},{"key":"ref7","doi-asserted-by":"crossref","volume-title":"Biotinidase deficiency","author":"B Wolf","DOI":"10.1016\/S0065-3101(24)00257-3"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/gim.2011.6","article-title":"Biotinidase deficiency: \u201cif you have to have an inherited metabolic disease, this is the one to have\u201d","volume":"14","author":"B Wolf","year":"2012","journal-title":"Genet Med"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"107560","DOI":"10.1016\/j.ymgme.2023.107560","article-title":"Biotinidase deficiency: what have we learned in forty years?","volume":"138","author":"A T Tankeu","year":"2023","journal-title":"Mol Genet Metab"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1542\/peds.68.1.113","article-title":"Multiple carboxylase deficiency: clinical and biochemical improvement following neonatal biotin treatment","volume":"68","author":"B Wolf","year":"1981","journal-title":"Pediatrics"},{"key":"ref11","first-page":"214","volume-title":"Vademecum Metabolicum, 5th Edition","author":"N Zschocke","year":"2021"},{"key":"ref12","volume-title":"Biotinidase Deficiency","author":"H Saleem"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"107610","DOI":"10.1016\/j.ymgme.2023.107610","article-title":"Complex metabolic disharmony in PMM2-CDG paves the way to new therapeutic approaches","volume":"139","author":"N Himmelreich","year":"2023","journal-title":"Mol Genet Metab"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s10545-011-9325-5","article-title":"Nijmegen paediatric CDG rating scale: a novel tool to assess disease progression","volume":"34","author":"S Achouitar","year":"2011","journal-title":"J Inherit Metab Dis"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0003-2697(89)90147-4","article-title":"The quantitation of biotinidase activity in dried blood spots using microtiter transfer plates: identification of biotinidase-deficient and heterozygous individuals","volume":"179","author":"D A Pettit","year":"1989","journal-title":"Anal Biochem"},{"key":"ref16","volume-title":"Adaptive behavior assessment system","author":"P L Harrison","year":"2003"},{"key":"ref17","first-page":"35","volume-title":"Assessing Psychological Functioning in Metabolic Disorders: Validation of the Adaptive Behavior Assessment System, Second Edition (ABAS-II), and the Behavior Rating Inventory of Executive Function (BRIEF) for Identification of Individuals at Risk","author":"S E Waisbren","year":"2015"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0009-8981(96)06396-6","article-title":"Biotinidase and its roles in biotin metabolism","volume":"255","author":"J Hymes","year":"1996","journal-title":"Clin Chim 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Metab"},{"issue":"02","key":"ref22","doi-asserted-by":"crossref","first-page":"101027","DOI":"10.1016\/j.gim.2023.101027","article-title":"Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions","volume":"26","author":"K Muthusamy","year":"2024","journal-title":"Genet Med"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s10339-024-01199-9","article-title":"Sex\/gender differences in general cognitive abilities: an investigation using the Leiter-3","volume":"25","author":"D Giofr\u00e8","year":"2024","journal-title":"Cogn Process"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2708-3016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:52:57Z","timestamp":1769125977000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2708-3016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":23,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2026,1,22]]},"published-print":{"date-parts":[[2026,2]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2708-3016","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]}}}