Clinical, biochemical characteristics and genotype-phenotype analysis of congenital hypothyroidism diagnosed by newborn screening in China

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients. The newborn screening was performed for TSH in dried blood spots. Serum TSH, T3, T4, free T3(FT3) and free T4 (FT4) were detected for the recalled children. High-throughput sequencing were applied to detect 29 known CH genes. The statistical analyses were performed to analyze the differences between biochemical data, thyroid volume, clinical prognosis and genetic results for 97 patients who had one or more variants in CH related genes. DUOX2 gene had the highest variant rate, followed by TG, TPO and TSHR gene. The “DUOX2 biallelic variants” group was associated with “Goiter”, while “DUOX2 monoallelic variants” group was associated with “Agenesis”. In addition, the TSH levels and initial L-T4 dose were significantly higher in “TPO biallelic variants” group than those in “DUOX2 and TSHR biallelic variants” groups. Our study showed dyshormonogenesis (DH) might be the leading pathophysiology of CH in Chinese populations. DUOX2 gene mostly caused goiter, but also could be associated with hypoplasia. TPO might play a more irreplaceable role than DUOX2. The digenic variants combination indicated the complexity of genetic etiology in CH.