IDENTIFICATION OF A HUMAN SERUM-ALBUMIN SPECIES ASSOCIATED WITH FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA

Familial dysalbuminemic hyperthyroxinemia (FDH) is a form of euthyroid hyperthyroxinemia that is due to an increased affinity of serum album in for T-4. Unlike the many physiologically neutral alloalbumins that have been identified by serum electrophoresis, FDH variants have not b een reproducibly resolved. In the present study, isoelectric focusing in the presence of the denaturants urea and Non-idet P-40, without red uction, produced two bands in the sera of unrelated FDH subjects in pl ace of each of the major albumin bands in the sera of normal subjects. One band of each FDH pair migrated with the normal band; the second m igrated at a slightly lower pi. The identity of the new bands as album in was confirmed by N-terminal sequencing. The two bands of each pair were present in approximately equal amounts, consistent with the autos omal dominant nature of the condition, the expectation that FDH indivi duals would be heterozygous for normal albumin (Alb-A), and evidence t hat high and normal affinity T-4-binding sites are equimolar or near e quimolar. Similar findings in sera from Hispanic and non-Hispanic FDH subjects suggest that the same structural change may underlie the FDH phenotype from different populations. The slightly lower pi of the FDH -specific bands is consistent with the His for Arg substitution predic ted by a G to A base transition recently reported in codon 218 of the gene for the variant albumin (Alb-FDH).