Inherited Decrease of the Binding Capacity of Thyroxine-Binding Globulin (Tbg)

Abstract

A family with a decrease in the binding capacity of thyroxine binding globulin (TBG) is described. The gene was probably transmitted by a female who married twice. Five subjects were considered TBG deficient, with TBG values ranging from 8.4 to 16.8 μg/100 ml. Of these subjects 2 were males and 3 females; the males had the lowest binding capacities. In addition, 1 male and 3 females had TBG values within the low normal range and were considered as possibly affected. The mode of inheritance could not be exactly defined but there were indications that it might be an autosomal dominant. The correlation of TBG to the protein-bound iodine in the serum (PBI), to the triiodothyronine uptake by Sephadex (T3-U), to the ratio between them (T3-U/PBI), and to the proportionate free thyroxine (PFT4) was strongly positive or negative. A gradual change in these variables from the affected to the unaffected subjects was observed. These correlations indicated that in normal subjects TBG is the most important factor governing the PBI and free thyroxine levels. In addition, a strong inverse and statistically significant correlation was observed between the binding capacity of TBG and that of the pre-albumin (TPBA). The difference between affected and unaffected subjects with regard to TPBA was also statistically significant.

Study of Four New Kindreds with Inherited Thyroxine-Binding Globulin Abnormalities POSSIBLE MUTATIONS OF A SINGLE GENE LOCUS

“…Each family presents a characteristic pattern. From our studies and those of others (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), we suggest that all TBG abnormalities in man so far described are probably X-chromosome-linked and manifested by quantitative variations in the serum concentration of an apparently structurally unaltered TBG. Mutations at a single locus controlling TBG synthesis could then explain the entire spectrum of genetic TBG abnormalities in man.…”

“…Similarly, the BMR (5,7,8,20,39), cholesterol (3,5,7,13,16,17,20,39,50,55,56), and thyroidal 'I uptake (3, 7, 10, 15-17, 20, 39, 50, 55-57) were within normal limits. No evidence for thyroid autoimmunity could be obtained from measurement of circulation thyroglobulin antibodies (5,11).…”

“…In only one family (L-6) TBPA levels appeared to have an inverse correlation with the TBG capacity (13). Similarly, other serum proteins including CBG (3,8,16,18) 6.7 7.1 TIME (min ) FIGURE 11 Rate of TBG inactivation at 60'C.…”

“…Criterion (g) was not completely satisfied in family G as the affected b'. was undoubtedly responsible for overlooking a typical X-linked inheritance pattern in at least two families (13,20). The pedigree of "family N" with high TBG satisfied criteria (a), (b), (e), (g), and most importantly (d).…”

“…The ability to identify the heterozygous ("carrier") state has helped establish X-chromosome-linked inheritance patterns in these families. Of the remaining nine families with diminished TBG, in eight, affected males had low but detectable TBG capacity (8)(9)(10)(11)(12)(13)(14), and in some instances "carrier" state in females could not be clearly identified because of overlap in their TBG capacity values with either affected males (8,9) or normals (13). Because of the presence of TBG in the hemizygous-affected subjects and inability to distinguish the heterozygous state with certainty, in three out of nine families, X-linked mode of inheritance was less obvious (8,9,12).…”