SAT450 High Diagnostic Yield Of NGS Analysis In Congenital Hypothyroidism With Thyorid Dyshormongenesis

Abstract

Abstract Disclosure: E. Joo: None. S. Kim: None. J. Lee: None. Introduction: Congenital hypothyroidism is the most common neonatal metabolic disorder and detected at a rate of 1 in 3000 to 4000 live births. 10-15 % of congenital hypothyroidism is caused by thyroid dyshormonogenesis. And Its clinical manifestations are individually different. Thus, to evaluate exact causes and predict clinical course for congenital thyroid dyshormonogenesis and establish precise strategies for treatment, we conduct Next-Generation Sequencing (NGS) to patients who diagnosed congenital hypothyroidism with normal thyroid gland and analysis the results. Methods: We conducted NGS to 31 patients patients who were diagnosed congenital hypothyroidism with normal contour of thyroid gland in ultrasonography from Jan. 2018 to April. 2022 in a single university hospital. We also analyzed their thyroid function test results, dose of levothyroxine and clinical manifestations. Result: Among the 31 patients, 25patients were detected from NGS. 4patients have oligogenic mutations. 7 DUOX2 variants were detected in 7 patients (22.6%), 3 DUOXA2 variants were detected in 4 patients (12.9%), 4 TSHR variants were detected in 7 patients (22.6%) 5 TG variants were detected in 4 patients (12.9%), 2 GLIS3 variants in 2 patients (6.5%), 1 TPO variants in 1 patient, 1 THRB variants in 1 patient, 1 NKX2-1 variants in 1 patient, 1 TRH variants in 1 patient, 1 SLC5A5 variants in 1 patient. The patients with GLIS3 stop levothyroxine at 3years old and have remission. The patients with DUOX2 variants and DUOXA2 variants showed low remission rate. DUOXA2 variants has high association with goiter. None of the patients with TSHR c.1349G>A mutation to stop medicine. But patients with other mutation of TSHR stop levothyroxine at 3 years old and have remission. None of the patients with TG variants showed remission. The patients with GLIS3 have remission at 3 years old. Conclusions: We cautiously recommend that using the NGS to strategize treatment plan for CH based on the clinical manifestations and genetic analysis of the family members of the index patients. Presentation: Saturday, June 17, 2023