The T4-binding
proteins of a euthyroid subject with persistent
hyperthyroxinemia (T4, greater than 20 micrograms/dl) were present in normal concentrations. Abnormal transport of both T4 and rT3 was demonstrated by reverse flow paper electrophoresis; excess T4 was bound to
albumin and
prealbumin, while increased binding of rT3 was confined to
prealbumin. The three T4-binding
proteins in the serum of the subject were isolated by affinity chromatography and characterized. Equilibrium dialysis experiments demonstrated a 20-fold increase in affinity of the
albumin for T4 (Ka, 5.1 X 10(6) M-1) and a 4-fold increase in affinity of
prealbumin for T4 (Ka, 3.0 X 10(8) M-1); T4-binding
globulin affinity was normal. Nine other members of the family were also studied. Two sisters of the propositus have both the abnormal
albumin and the variant
prealbumin, while a brother has normal T4-binding
proteins. The mother has the abnormal
albumin alone. The father, his sister, and one of his three brothers have the variant
prealbumin only. Despite the presence of the variant
prealbumin in some of the paternal relatives of the propositus, their total iodothyronine concentrations were within the normal ranges; the condition may, therefore, often go undetected. The characteristics of the
albumin found in the affected members of this kindred are those we have defined for
familial dysalbuminemic hyperthyroxinemia type I, which is inherited as an autosomal dominant trait. The pattern of inheritance of the variant
prealbumin is also consistent with a dominant mode with strong penetrance. The presence of two separately inherited abnormal T4
transport proteins in the same family suggests that both conditions may be more common than has been thought.