Thyroxine-binding globulin deficiencydetected by newborn screening

We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroixine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T₄), trliodothyronine resin uptake (T₃RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T₄ level <38.6 nmol/L (3 μg/dl) or a T₄ level <3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T₄ concentration for TBG-deficlent boys was 41.9 nmol/L (3.26 μg/dl); 31% had values <25.7 nmol/L (2.0 μg/dl). The mean serum T₄ concentration for TBG-deficient giris was 60.2 nmol/L (4.68 μg/dl), with none <2.0 μg/dl. The mean T₃RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T₃RU value was >0.55 in 24% of TBG-deficient boys but was >0.55 in only one girl. Free serum T₄ levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T₄ and T₃RU values, but severe deficiency is rare in girls.