title: Analysis of thiamine transporter genes in sporadic beriberi.
abstract: OBJECTIVE
  Thiamine or vitamin B1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3, and SLC25 A19, in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency.
  
  
  METHODS
  A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B1 serum levels, his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment, suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database.
  
  
  RESULTS
  Thirty-seven mutations were tested: 29 in SLC19 A2, 6 in SLC19 A3, and 2 in SLC25 A19. Mutational analyses showed a wild-type genotype for all sequences investigated.
  
  
  CONCLUSIONS
  This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations, in the same genes or in other thiamine-associated genes, in the occurrence of this nutritional neuropathy.
authors.affiliation: Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bravatà
authors.affiliation: Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Minafra
authors.affiliation: U.O. Neurologia, Fondazione Istituto "San Raffaele-G. Giglio", Cefalù PA, Scilly, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Callari
authors.affiliation: Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
authors.affiliation: U.O. Neurologia, Fondazione Istituto "San Raffaele-G. Giglio", Cefalù PA, Scilly, Italy. Electronic address: Luigi.grimaldi@hsr.it.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Edoardo Grimaldi
mesh_terms: D000328:Adult; D000437:Alcoholism; D001602:Beriberi / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins; D009154:Mutation; D013831:Thiamine / Q000235:genetics*; D013832:Thiamine Deficiency / Q000150:complications / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; C434255:SLC25A19 protein, human; D013831:Thiamine
keywords: Beriberi; Mutations; SLC19 A2; SLC19 A3; SLC25 A19; Thiamine