Familial dysalbuminemic hypertriiodothyroninemia: A new, dominantly inherited albumin defect

• Main Authors: Thongkum Sunthornthepvarakul, Supawadee Likitmaskul, Supunnee Ngowngarmratana, Kitti Angsusingha, Sureerat Kitvitayasak, Neal H. Scherberg, Samuel Refetoff
• Other Authors: Rajavithi Hospital
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/18284
• Institution: Mahidol University

We report the abnormal albumin in members of a Thai family that presented with high serum total T3but not T4when measured by radioimmunoassay. In contrast, total T3values were very low when measured by ELISA and chemiluminescence. The subjects have no goiter, and clinically euthyroid. Their serum free T4, free T3, and TSH were normal. Spiking of T3to affected serum showed good recovery by radioimmunoassay but very poor recovery by ELISA and by chemiluminescence. The immunoprecipitation with labeled T3bound to albumin showed high percent precipitation in affected serum. T3- binding studies showed that the association constant of serum albumin in affected subjects was 1.5 x 106M-1or 40-fold that of unaffected relatives of 3.9 x 104M-1. In contrast, the K(a) of HSA for T4in an affected subject was only 1.5-fold that of a normal. Albumin complementary DNA from leukocytes of affected member was amplified and sequenced. We found the second nucleotide of normal codon 66 (CTT), a thymine, was substituted by a cytosine (CCT), resulting in the replacement of the normal leucine by proline. This is the first report of variant albumin causing familial dysalbuminemic hypertriiodothyroninemia.