Biocruces Health Research Institute, Cruces University Hospital, CIBERER, CIBERDEM, UPV-EHU, Barakaldo, Basque Country, Spain.
Biocruces Health Research Institute, Alto Deba Hospital, Gipuzkoa, Basque Country, Spain.
J Endocrinol Invest. 2019 Aug;42(8):941-949. doi: 10.1007/s40618-019-1007-4. Epub 2019 Feb 1.
Thyroid hormone resistance (RTH β) is a rare genetic disorder characterized by an altered response of target tissue to the action of thyroid hormone. Few studies on RTH β have been carried out in southern European populations. We aimed to describe the clinical and genetic characteristics at the time of diagnosis in a Spanish cohort of patients with genetically confirmed RTH β, with ages ranging from newborns to adults.
Retrospective multicenter study of 28 patients who were genetically confirmed as RTH β. Clinical and biochemical data were collected from the reference centers, and the studied variables included age, sex, anthropometric data, clinical characteristics and biochemical results. In the Basque country, a simultaneous analysis of TSH and T4 is carried out in the program for the screening of inborn errors of metabolism. A molecular analysis of the thyroid hormone beta (THRB) gene was performed.
The total cohort included 20 adults and eight pediatric patients (six newborns). Of the total, 5 (17.8%) were diagnosed by clinical characteristics (goiter, hypertension or tachycardia), 13 (46.4%) were analyzed in the context of a family study and 10 (35.7%) were diagnosed after obtaining an altered fT4 and/or TSH level in a biochemical analysis performed due to clinical symptoms unrelated to RTH β. Four of the newborns included in the series were diagnosed by the result of neonatal screening, which allows us to estimate a minimum local incidence of RTH β of 1/18,750 live newborns. The genetic analysis showed the presence of 12 different heterozygous mutations in the THRB gene.
We report the clinical and genetic characteristics of a Spanish RTH β cohort, from neonates to adults. We also describe one novel mutation in the THRB gene as the cause of the disease. The simultaneous analysis of TSH and T4 carried out in the program for the screening of inborn errors of metabolism facilitates the early diagnosis of RTH β in newborns and has allowed us to estimate a minimum local incidence of RTH of 1/18,750 live newborns.
甲状腺激素抵抗（RTHβ）是一种罕见的遗传性疾病，其特征是靶组织对甲状腺激素作用的反应发生改变。在南欧人群中，对 RTHβ 的研究较少。我们旨在描述经基因证实的 RTHβ西班牙患者队列在诊断时的临床和遗传特征，年龄从新生儿到成人不等。
对 28 名经基因证实为 RTHβ的患者进行回顾性多中心研究。从参考中心收集临床和生化数据，研究变量包括年龄、性别、人体测量数据、临床特征和生化结果。在巴斯克地区，同时对 TSH 和 T4 进行分析，以筛查先天性代谢错误。对甲状腺激素β（THRB）基因进行了分子分析。
总队列包括 20 名成人和 8 名儿科患者（6 名新生儿）。其中，5 例（17.8%）通过临床特征（甲状腺肿、高血压或心动过速）诊断，13 例（46.4%）在家族研究中分析，10 例（35.7%）在生化分析中因与 RTHβ无关的临床症状而改变 fT4 和/或 TSH 水平后诊断。系列中包括的 4 名新生儿通过新生儿筛查结果诊断，这使我们能够估计 RTHβ的局部最低发生率为每 18750 名活产儿 1 例。基因分析显示 THRB 基因存在 12 种不同的杂合突变。
我们报告了一个西班牙 RTHβ 队列的临床和遗传特征，从新生儿到成人。我们还描述了 THRB 基因中的一个新突变是导致该疾病的原因。同时对 TSH 和 T4 进行分析，在先天性代谢错误筛查计划中进行，便于新生儿 RTHβ的早期诊断，并使我们能够估计 RTHβ的局部最低发生率为每 18750 名活产儿 1 例。
