Inherited X chromosome linked thyroxine-binding globulin (TBG) deficiency in a homozygous female

Abstract

Of the 37 families with TBG deficiency so far described, 31 were shown to be compatible with X chromosome linked mode of inheritance, and in 5 of the remaining 6 this mode of transmission was suspected. Difficulties in proving X chromosome linkage in some families was usually due to the inability to identify the heterozygous female carriers when affected males were only partially TBG deficient. This work describes a new family with inherited TBG deficiency which on first glance showed inconsistencies with X chromosome linked inheritance. More specifically, there was an apparent male to male transmission of the trait and the presentation in one female of low TBG, phenotypically indistinguishable from the affected males. Studies on three generations identified TBG deficiency on both the maternal and paternal branches of the family. We were thus able to prove that the affected male inherited the trait from his heterozygous mother, rather than from his father, and that the female with more severe TBG deficiency was homozygous for the trait through acquisition of a defective X chromosome from both mother and father. The latter explained her phenotype presentation indistinguishable from that in affected hemizygous males. Thus, unless proven otherwise, all inherited TBG abnormalities in man appear to be X chromosome linked. Because of the relatively common prevalence of inherited TBG defects, marriages among such individuals are expected to give rise to a progeny with an unusual phenotypic presentation. All members of the family were clinically euthyroid and affected members showed a normal TSH response to TRH.