Lalloz M R, Byfield P G, Goel K M, Loudon M M, Thomson J A, Himsworth R L
J Clin Endocrinol Metab. 1987 Feb;64(2):346-52. doi: 10.1210/jcem-64-2-346.
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.
一名甲状腺功能正常但甲状腺素持续升高（T4大于20微克/分升）的受试者，其T4结合蛋白浓度正常。通过反流纸电泳证明了T4和反T3（rT3）的转运异常；过量的T4与白蛋白和前白蛋白结合，而rT3结合增加仅限于前白蛋白。通过亲和层析分离并鉴定了该受试者血清中的三种T4结合蛋白。平衡透析实验表明，白蛋白对T4的亲和力增加了20倍（Ka，5.1×10⁶M⁻¹），前白蛋白对T4的亲和力增加了4倍（Ka，3.0×10⁸M⁻¹）；T4结合球蛋白的亲和力正常。还研究了该家族的其他九名成员。先证者的两个姐妹同时具有异常白蛋白和变异前白蛋白，而一个兄弟的T4结合蛋白正常。母亲仅具有异常白蛋白。父亲、他的妹妹以及他三个兄弟中的一个仅具有变异前白蛋白。尽管先证者的一些父系亲属中存在变异前白蛋白，但他们的总碘甲状腺原氨酸浓度在正常范围内；因此，这种情况可能经常未被发现。在这个家族的患病成员中发现的白蛋白特征是我们为I型家族性异常白蛋白血症性甲状腺素过多症所定义的特征，该病症作为常染色体显性性状遗传。变异前白蛋白的遗传模式也与具有强外显率的显性模式一致。同一家族中存在两种分别遗传的异常T4转运蛋白表明，这两种情况可能比人们想象的更为常见。
