This study describes a family with intrinsic thyroid disease in addition to familial dysalbuminemic hyperthyroxinemia, a syndrome associated with euthyroidism and increased binding of thyroxine to serum albumin.
Here we show linkage between FDH and the albumin gene in a large Amish family of Swiss descent, using as markers a SacI polymorphism in the coding sequence of the albumin gene and the group-specific component (Gc) gene, located less than 1 centimorgan from the albumin gene.
An individual with familial dysalbuminemic hyperthyroxinemia (FDH) due to a homozygous mutation (c.653G>A, p.R218H) in the human serum albumin (HSA) gene is reported.
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).
DNA analysis of the patient revealed R218H, a mutation in the serum albumin gene associated with FDH, which was also present in the patient's euthyroid father and brother.
Familial dysalbuminemic hyperthyroxinemia in a Swiss family caused by a mutant albumin (R218P) shows an apparent discrepancy between serum concentration and affinity for thyroxine.
In this study a protein expression system was used to synthesize recombinant human serum albumin containing a mutation that has been shown to result in familial dysalbuminemic hyperthyroxinemia.
In all FDH-affected Caucasian subjects from 10 unrelated families with a moderate increase in serum T4, the guanine to adenine transition was demonstrated at the same position of the albumin gene as noted in our patients, but histidine, the replacement amino acid, differed from proline noted in our FDH Japanese subjects.
The diagnosis of familial dysalbuminaemic hyperthyroxinaemia was confirmed by the detection of a guanine to adenine missense mutation in the second nucleotide of codon 218 of the gene encoding human serum albumin, showing that the mutation in this family is the same as that previously found in Caucasian populations.
A Chinese Family with Familial Dysalbuminemic Hyperthyroxinemia (FDH) due to R242H Mutation on Human Albumin Gene: Reevaluating the Role of FDH in Patients with Asymptomatic Hyperthyroxinemia.
Treatment of FDH patients with other drugs may require an altered dosage if the drug binds to the atypical albumin fragments characterizing this disorder.
The diagnosis of FDH in these two patients was obscured, and probably would not have been made were it not for the present investigation, which led to the electrophoretic demonstration of increased binding of T4 by serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine whether thyroid hormone-binding proteins in serum, particularly albumin, facilitate the transfer of T4 into human tissues, we studied cellular T4 uptake (CT4) by human liver (Hep G2) cells from medium containing serum from subjects with familial dysalbuminemic hyperthyroxinemia (FDH) and acquired and familial T4-binding globulin (TBG) excess and patients with normal T4-binding to albumin and normal TBG concentrations.