Familial dysalbuminemic hyperthyroxinemia (FDH) is an inherited disease characterized by increased circulating total thyroxine (T4) levels and normal physiological thyroid function. Heterozygous albumin gene (ALB) variants have been reported to be the underlying cause of FDH. To our knowledge, there have been no confirmed FDH cases in Korea. We recently observed a female patient with mild T4 elevation (1.2 to 1.4-fold) and variable levels of free T4 according to different assay methods. Upon Sanger sequencing of her ALB, a heterozygous c.725G>A (p.Arg242His) variant was identified. The patient's father and eldest son had similar thyroid function test results and were confirmed to have the same variant. Although the prevalence of FDH might be very low in the Korean population, clinical suspicion is important to avoid unnecessary evaluation and treatment.
Adult ; Albumins/*genetics ; Base Sequence ; Female ; Heterozygote ; Humans ; Hyperthyroxinemia, Familial Dysalbuminemic/*genetics ; Pedigree ; Radioimmunoassay ; Sequence Analysis, DNA ; Thyroxine/analysis

OBJECTIVETo report a family of familial dysalbuminaemic hyperthyroxinaemia(FDH).

METHODSFour members, including the female proband, mother, daughter and brother, went through the measurement of thyroid hormone and thyroid-stimulating hormone (TSH). Electrophoretic analysis of the patient's serum proteins was carried out after the patient's serum being incubated with fluorescein isothiocyanate (FITC) labeled thyroxine(T4), The point mutation of Alb gene was determined in all members.

RESULTSThe measurements of thyroid hormane and TSH showed that in three members (the proband, her mother and her daughter), the total thyroxine(TT4) serum level was high, the total triiodothyronine(TT3), FT4, FT3 and TSH serum levels were normal. And the enhanced albumin binding of fluorescenced T4 by electrophoresis showed a mutation transition 653 G-->A on DNA coding region of albumin. But in the proband's brother, the thyroid function and the results of electrophoresis of thyroxine-binding protein and determination of albumin gene were normal.

CONCLUSIONA family with FDH in China is firstly reported here, a mutation at albumin gene DNA coding region 653G-->A causing enhanced albumin binding of T4 results in high T4 level.

Adult ; Base Sequence ; DNA Mutational Analysis ; Family Health ; Female ; Humans ; Hyperthyroxinemia, Familial Dysalbuminemic ; blood ; genetics ; Male ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Thyrotropin ; blood ; Thyroxine ; blood ; Thyroxine-Binding Proteins ; genetics ; Triiodothyronine ; blood