FAMILIAL DYSALBUMINEMIC HYPERTRIIODOTHYRONINEMIA - A NEW, DOMINANTLY INHERITED ALBUMIN DEFECT

We report the abnormal albumin in members of a Thai family that presen ted with high serum total T-3 but not T-4 when measured by radioimmuno assay. In contrast, total T-3 values were very low when measured by EL ISA and chemiluminescence. The subjects have no goiter, and clinically euthyroid. Their serum free T-4, free T-3, and TSH were normal. Spiki ng of T-3 to affected serum showed good recovery by radioimmunoassay, but very poor recovery by ELISA and by chemiluminescence. The immunopr ecipitation with labeled T-3 bound to albumin showed high percent prec ipitation in affected serum. T-3-binding studies showed that the assoc iation constant of serum albumin in affected subjects was 1.5 X 10(6) M-1 or 40-fold that of unaffected relatives of 3.9 x 10(4) M-1. In con trast, the K-a of HSA for T-4 in an affected subject was only 1.5-fold that of a normal. Albumin complementary DNA from leukocytes of affect ed member was amplified and sequenced. We found the second nucleotide of normal codon 66 (CTT), a thymine, was substituted by a cytosine (CC T), resulting in the replacement of the normal leucine by proline. Thi s is the first report of variant albumin causing familial dysalbuminem ic hypertriiodothyroninemia.