title: Selenium supplementation fails to correct the selenoprotein synthesis defect in subjects with SBP2 gene mutations.
abstract: BACKGROUND
  Selenium (Se) is an essential trace element needed for the biosynthesis of selenoproteins. Selenocysteine incorporation sequence binding protein 2 (SBP2) represents a key trans-acting factor for the co-translational insertion of selenocysteine into selenoproteins. We recently described children with mutations in the SBP2 gene who displayed abnormal thyroid function tests and reduced selenoprotein concentrations. We have tried to improve selenoprotein biosynthesis and thyroid hormone metabolism in SBP2 deficient subjects by supplementing an organic and an inorganic Se form.
  
  
  METHODS
  Three affected and two unaffected siblings received daily doses of 100, 200, or 400 microg selenomethionine-rich yeast and 400 microg sodium selenite for one month each. Serum was drawn at baseline and after supplementations. Thyroid function tests, extracellular glutathione peroxidase activity, Se, and selenoprotein P concentrations were determined.
  
  
  RESULTS
  Selenomethionine-rich yeast increased serum Se concentrations in all subjects irrespective of genotype. Sodium selenite was effective in increasing the selenoprotein P concentration in normal and to a lesser degree in affected subjects. Both forms failed to increase the glutathione peroxidase activity or to correct the thyroid function abnormalities in the SBP2 deficient individuals indicating that impaired deiodinase expression was not positively affected. No adverse side effects were observed.
  
  
  CONCLUSIONS
  Total serum Se concentrations in SBP2 deficient subjects respond to selenomethionine supplementation but this effect is not indicative for improved selenoprotein synthesis. Se is obviously not a limiting factor in the SBP2 deficient individuals when regular daily Se intake is provided. These findings might help to identify and diagnose more individuals with selenoprotein biosynthesis defects who might present at young age irrespective of their Se supply with characteristic thyroid function test abnormalities, growth retardation, and reduced Se and selenoprotein concentrations.
authors.affiliation: Institute for Experimental Endocrinology, Charité-University Medicine Berlin, Berlin, Germany. lutz.schomburg@charite.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Dumitrescu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liao
authors.forename: Bassam
authors.initials: B
authors.lastname: Bin-Abbas
authors.forename: Johanna
authors.initials: J
authors.lastname: Hoeflich
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D004032:Diet; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000502:physiology*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*; D012643:Selenium / Q000008:administration & dosage / Q000627:therapeutic use*; D051140:Selenoproteins / Q000096:biosynthesis* / Q000235:genetics*; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000975:Antioxidants; D016601:RNA-Binding Proteins; C121530:SECISBP2 protein, human; D051140:Selenoproteins; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D012643:Selenium; D013974:Thyroxine