Familial dysalbuminemic hyperthyroxinemia (FDH) is a form of euthyroid hyperthyroxinemia that is due to an increased affinity of serum albumin for T4. Unlike the many physiologically neutral alloalbumins that have been identified by serum electrophoresis, FDH variants have not been reproducibly resolved. In the present study, isoelectric focusing in the presence of the denaturants urea and Nonidet P-40, without reduction, produced two bands in the sera of unrelated FDH subjects in place 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 migrated at a slightly lower pI. The identity of the new bands as albumin was confirmed by N-terminal sequencing. The two bands of each pair were present in approximately equal amounts, consistent with the autosomal dominant nature of the condition, the expectation that FDH individuals would be heterozygous for normal albumin (Alb-A), and evidence that high and normal affinity T4-binding sites are equimolar or near equimolar. 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 predicted by a G to A base transition recently reported in codon 218 of the gene for the variant albumin (Alb-FDH).
Detergents Electrophoresis, Polyacrylamide Gel