Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6

摘要

Biotin, pantothenate and lipoate-dependent metabolic pathways and the effect of identified variants in SLC5A6. Pedigree of the non-consanguineous family. Chromatograms from Sanger sequencing of patient DNA compared to cDNA show decreased expression of the V141Afs*34 allele and stable expression of the R400T allele. Uptake of radiolabelled biotin by HeLa cells transfected with empty vector, wild-type or mutant SMVT expression constructs. Uptake by mutant constructs is decreased compared to wild-type (  = 0.008) and not significantly different to empty vector (  > 0.05). Data show the mean and standard error of the mean (  = 4). SCL5A6 function and Enzymes for which the vitamins Biotin (green), Pantothenate (blue) and Alpha-lipoic acid (red) play a role as important cofactors in: the degradation pathways of the amino acids leucine, isoleucine, valine and glycine; glucose energy metabolism; the TCA cycle; and fatty acid oxidation metabolism. All pathways apart from the glycine cleavage system play a fundamental role in cellular energy production. The pathways involved with fatty acid metabolism and branch chain amino acid breakdown occur almost exclusively in the liver. BBB blood–brain barrier, BCKD Branch chain ketoacid dehydrogenase, CNS central nervous system, KDHC ketoglutarate dehydrogenase complex, PC pyruvate carboxylase, PCC propionyl-CoA carboxylase, PDHC pyruvate dehdrogenase complex, 3MCCC 3-methyl crotonyl-CoA carboxylase