{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:27:00Z","timestamp":1791563220919,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"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":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The sodium\u2010dependent multivitamin transporter (<jats:styled-content style=\"fixed-case\">SMVT<\/jats:styled-content>) is a ubiquitously expressed sodium\u2010solute symporter that transports pantothenic acid, biotin, and \u03b1\u2010lipoic acid across the intestinal epithelia and blood\u2013brain barrier. Severe biallelic loss\u2010of\u2010function variants in <jats:styled-content style=\"fixed-case\">\n<jats:italic>SLC5A6<\/jats:italic>\n<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">MIM<\/jats:styled-content> #604024) lead to <jats:styled-content style=\"fixed-case\">SMVT<\/jats:styled-content> deficiency (<jats:styled-content style=\"fixed-case\">SMVTD<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">MIM<\/jats:styled-content> #618973), which classically presents with developmental delay, brain atrophy, epilepsy, sensorineural hearing loss, peripheral neuropathy, and gastrointestinal, cutaneous, and immunologic abnormalities. We describe a 25\u2010year\u2010old female with autism spectrum disorder (<jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>), intellectual disability, agenesis of the corpus callosum (<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>), and epilepsy who presented at 15\u2009years of age with a severe metabolic crisis characterized by hyperammonemia, lactic acidosis, and rhabdomyolysis. Trio exome sequencing (<jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content>) identified compound heterozygous variants in <jats:styled-content style=\"fixed-case\">\n<jats:italic>SLC5A6<\/jats:italic>\n<\/jats:styled-content>. Plasma untargeted metabolomics analysis demonstrated reduced pantothenate and coenzyme A with elevated long\u2010chain fatty acids, indicating impaired fatty acid oxidation, functionally validating <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> results, and confirming a diagnosis of <jats:styled-content style=\"fixed-case\">SMVTD<\/jats:styled-content>. Targeted replacement with biotin, lipoic acid, and pantothenic acid improved her neurocognitive function and metabolic control. Our patient, the oldest reported at diagnosis, expands the phenotype of <jats:styled-content style=\"fixed-case\">SMVTD<\/jats:styled-content> to include rhabdomyolysis, <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>. Our study suggests that integrating <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> and untargeted metabolomics in undiagnosed patients with suspected inborn errors of metabolism may help identify this ultra\u2010rare disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.64014","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T12:04:31Z","timestamp":1738584271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expanded Clinical Phenotype and the Role of Untargeted Metabolomics Analysis in Confirming the Diagnosis of Sodium\u2010Dependent Multivitamin Transporter Deficiency"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3248-0761","authenticated-orcid":false,"given":"Ameya S.","family":"Walimbe","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Waskow","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Miller","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charul","family":"Gijavanekar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Difalco","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H.","family":"Elsea","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-8460","authenticated-orcid":false,"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"BCM\u2010CUHK Center of Medical Genetics, Prince of Wales Hospital 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