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Currently, four genetic defects have been described causing impairment of thiamine transport and metabolism: SLC19A2 dysfunction leads to diabetes mellitus, megaloblastic anemia and sensory\u2010neural hearing loss, whereas SLC19A3, SLC25A19, and TPK1\u2010related disorders result in recurrent encephalopathy, basal ganglia necrosis, generalized dystonia, severe disability, and early death. In order to achieve early diagnosis and treatment, biomarkers play an important role. <jats:italic>SLC19A3<\/jats:italic> patients present a profound decrease of free\u2010thiamine in cerebrospinal fluid (CSF) and fibroblasts. <jats:italic>TPK1<\/jats:italic> patients show decreased concentrations of thiamine pyrophosphate in blood and muscle. Thiamine supplementation has been shown to improve diabetes and anemia control in Rogers' syndrome patients due to SLC19A2 deficiency. In a significant number of patients with <jats:italic>SLC19A3<\/jats:italic>, thiamine improves clinical outcome and survival, and prevents further metabolic crisis. In <jats:italic>SLC25A19<\/jats:italic> and <jats:italic>TPK1<\/jats:italic> defects, thiamine has also led to clinical stabilization in single cases. Moreover, thiamine supplementation leads to normal concentrations of free\u2010thiamine in the CSF of SLC19A3 patients. Herein, we present a literature review of the current knowledge of the disease including related clinical phenotypes, treatment approaches, update of pathogenic variants, as well as in vitro and in vivo functional models that provide pathogenic evidence and propose mechanisms for thiamine deficiency in humans.<\/jats:p>","DOI":"10.1002\/jimd.12125","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T18:48:20Z","timestamp":1558032500000},"page":"581-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5762-4023","authenticated-orcid":false,"given":"Anna","family":"Marc\u00e9\u2010Grau","sequence":"first","affiliation":[{"name":"Pediatric Neurology Research Group Hospital Vall 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