A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia

Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant di sorder characterized by euthyroid hyperthyroxinemia. However, FDH has not b een reported in Chinese or African patients. Here, we report the first case of FDH in a Chinese patient. A 69-year-old Chinese man was found to have i ncreased serum total T-4 concentrations (198-242 nmol/l; normal range 58-14 8 nmol/l) and free T-4 concentrations (>58 pmol/l, T-4 analog method, norma l range 9-28 pmol/l). Serum total T-3 and TSH concentrations were normal. T he patient was misdiagnosed as hyperthyroid and was later suspected to have a TSH-producing tumor by the finding of a pituitary microadenoma, which wa s eventually proven to be a non-functional pituitary 'incidentaloma'. Elect rophoretic analysis of the patient's serum proteins demonstrated enhanced a lbumin binding of [I-125]T-4. Serum free TS concentrations were normal (16- 19 pmol/l, normal range 9-26 pmol/l) when a two-step method was used. Direc t sequencing of the albumin gene showed a guanine to adenosine transition i n the second nucleotide of codon 218, resulting in a substitution of histid ine (CAC) for the normal arginine (CGC) in one of the two alleles in the pa tient. The point mutation was further confirmed by HphI digestion of exon 7 of the albumin gene. The patient's son was not affected. Our studies demon strated that the point mutation of the albumin gene in a Chinese patient wi th FDH was similar to that found in western white families, but differed fr om that in a Japanese family in whom a guanine to cytosine transition at th e same position was found.