Monalisa Ferreira Azevedo
A NOVEL SYNDROME RELATED TO SELENOPROTEINS DEFICIENCY Azevedo, MF1,3; Barra, GB2; Castro, LC1; Amato, AA1,3; Velasco LFR2; Godoy, P2; Naves, LA3; Neves, FAR1
1 Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília – UnB, Brasília, DF, Brazil. 2 Sabin Institute and Laboratory of Clinical Analysis, Brasilia, DF, Brazil. 3 Section of Endocrinology, University Hospital of Brasilia, Faculty of Medicine, University of Brasilia - UnB, Brasilia, DF, Brazil.
The generation of active thyroid hormone or its inactivation is mediated by deiodinases. The synthesis of these enzymes requires incorporation of the rare aminoacid selenocysteine, through recoding of the UGA stop codon, in a unique process that creates the class of selenoproteins. The recognition of UGA requires a selenocysteine insertion sequence (SECIS) element in the 3’ untranslated region, and is mediated by the SECIS binding protein (SBP2). We describe a 11-year-old girl who presented with thyroid hormone dysfunction associated with short stature, delayed bone age, defective auditory function, progressive peripheral myopathy characterized by hypotonia and weakness, and moderate scoliosis with lateral trunk deviation. Serum TSH was slightly increased, with elevated T4 and reverse T3, while T3 levels were low. Low doses of T3 supplementation, but not T4, suppressed TSH. These findings suggest an impairment of the conversion of T4 to T3. Further analysis showed that the patient’s serum levels of another selenoprotein, glutathione peroxidase (GPx), were significantly reduced (GPx 11 U/g Hb; Normal Range 27.5 – 73.5 U/g Hb). Moreover, serum selenium was undetectable (Normal Range 50 –150 mg/L). Genetic investigation demonstrated two novel nonsense heterozygous mutations affecting the SBP2 gene that create a truncated protein (R120X/R770X). Family investigation showed that inheritance is recessive. Since SBP2 is epistatic to selenoproteins synthesis, these mutations produced a generalized defect on selenoproteins, with a phenotype that had not been previously described. The description of this novel syndrome comprises a new perspective on the comprehension of the physiological role of selenoproteins in humans.