Introduction: Neonatal screening programs for congenital hypothyroidism (CH) have been implemented worldwide to facilitate early diagnosis and treatment. The Dutch neonatal CH screening is primarily based on the measurement of thyroxine (T4). When T4 is low, an additional thyroxine-binding globulin (TBG) measurement is performed to reduce the number of false-positive screening results due to harmless TBG deficiency. Here, we present a case of a rare functional TBG deficiency leading to a false suspicion of CH. Case Presentation: Neonatal screening in this patient revealed a decreased T4, normal TSH, and normal TBG concentration, suggesting central CH. However, free T4 was normal. DNA sequencing analysis revealed a novel, hemizygous mutation (c.139G#x3e;A) in SERPINA7, the gene encoding TBG, resulting in the substitution of the conserved amino acid alanine to threonine at position 27. Crystal structure analyses showed that this substitution has a detrimental effect on binding of T4 to TBG. Conclusions: The novel SERPINA7 variant in this patient led to a false suspicion of central hypothyroidism in the Dutch T4-based neonatal screening program. It is important to recognize patients with such TBG defects to prevent unnecessary additional testing and treatment.
Horm Res Paediatr

中文翻译：

---

一例低结合亲和力突变的甲状腺素结合球蛋白误诊先天性甲状腺功能减退症新生儿

简介：先天性甲状腺功能减退症 (CH) 的新生儿筛查计划已在世界范围内实施，以促进早期诊断和治疗。荷兰新生儿 CH 筛查主要基于甲状腺素 (T4) 的测量。当 T4 较低时，会进行额外的甲状腺素结合球蛋白 (TBG) 测量，以减少由于无害 TBG 缺乏而导致的假阳性筛查结果的数量。在这里，我们介绍了一个罕见的功能性 TBG 缺陷导致对 CH 的错误怀疑的案例。病例介绍：该患者的新生儿筛查显示 T4 降低、TSH 和 TBG 浓度正常，提示中枢性 CH。然而，游离T4是正常的。在; DNA测序分析揭示一种新颖的，半合子突变（A c.139G＃x3e） SERPINA7，编码TBG的基因，导致保守氨基酸丙氨酸在位置27处替换为苏氨酸。晶体结构分析表明这种替换对T4与TBG的结合具有不利影响。结论：该患者的新型SERPINA7变异导致在基于荷兰 T4 的新生儿筛查计划中误怀疑中枢性甲状腺功能减退症。识别具有此类 TBG 缺陷的患者以防止不必要的额外检查和治疗非常重要。
儿科研究