{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:47:06Z","timestamp":1762674426110,"version":"3.40.5"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Classic homocystinuria is due to deficiency of cystathionine beta\u2010synthase (CBS), a pyridoxine\u2010dependent enzyme that, depending on the molecular variants, may be co\u2010factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I\/III heterozygotes. Our state has implemented a two\u2010tier NBS algorithm for CBSD that successfully reduced the number of MATI\/III heterozygotes, yet effectively detected a mild, co\u2010factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high\u2010dose pyridoxine to determine responsiveness. Here we describe our NBS\u2010identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight\u2010based dosing and duration recommendations for pyridoxine challenge in neonates.<\/jats:p>","DOI":"10.1002\/ajmg.a.61815","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T11:54:06Z","timestamp":1598010846000},"page":"2704-2708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A cautionary tale of pyridoxine toxicity in cystathionine beta\u2010synthase deficiency detected by two\u2010tier newborn screening highlights the need for clear pyridoxine dosing guidelines"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0428-1909","authenticated-orcid":false,"given":"Elizabeth G.","family":"Ames","sequence":"first","affiliation":[{"name":"Division of Pediatric Genetics, Metabolism, and Genomic Medicine, Department of Pediatrics University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Metabolism, and Genomic Medicine, Department of Pediatrics University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara B.","family":"Pappas","sequence":"additional","affiliation":[{"name":"Division of Genetic, Genomic, and Metabolic Disorders Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn M.","family":"Moloney","sequence":"additional","affiliation":[{"name":"Metabolic Newborn Screening Laboratory, Bureau of Laboratories, Michigan Department of Health and Human Services  Lansing Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Conway","sequence":"additional","affiliation":[{"name":"Division of Genetic, Genomic, and Metabolic Disorders Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Metabolism, and Genomic Medicine, Department of Pediatrics University of Michigan Health System  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1007\/8904_2011_109"},{"doi-asserted-by":"publisher","key":"e_1_2_7_3_1","DOI":"10.1007\/978-3-642-40337-8"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1056\/NEJM199905133401915"},{"doi-asserted-by":"publisher","key":"e_1_2_7_5_1","DOI":"10.1136\/jcp.17.4.427"},{"doi-asserted-by":"publisher","key":"e_1_2_7_6_1","DOI":"10.1007\/s10545-015-9830-z"},{"key":"e_1_2_7_7_1","first-page":"47","article-title":"Lysine\u2010restricted diet as adjunct therapy for pyridoxine\u2010dependent epilepsy: The PDE consortium consensus recommendations","volume":"15","author":"Karnebeek C. 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