Abstract
Thiamine is a water-soluble vitamin acting, in the mitochondria, as a cofactor for energy metabolism and, in the cytoplasm, in the pentose phosphate biosynthetic pathway. Its transport through the plasma membrane requires two transporters with overlapping functions: THTR1 encoded by SLC19A2 and THTR2 encoded by SLC19A3. Thiamine is transformed into its active form, thiamine pyrophosphate (TPP), by a kinase encoded by the TPK1 gene. Then it may enter the mitochondrial through a TPP transporter encoded by SLC25A19. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anemia (TRMA) characterized by megaloblastic anemia, progressive deafness, and diabetes mellitus eventually associated with optic neuropathy. Mutations in SLC19A3 cause biotin-/thiamine-responsive basal ganglia disease characterized by episodes of severe Leigh-like encephalopathy often triggered by fever that respond to a combination of biotin and thiamine. Mutations in SLC25A19 may cause early microcephaly with death in infancy (also called Amish microcephaly) or a later-onset bilateral striatal necrosis with progressive peripheral neuropathy. Recently, mutations in the TPK1 gene have been associated with recurrent encephalopathy with mild lactic acidosis.
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Sedel, F. (2014). Thiamine Disorders. In: Blau, N., Duran, M., Gibson, K., Dionisi Vici, C. (eds) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40337-8_15
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DOI: https://doi.org/10.1007/978-3-642-40337-8_15
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