ESPE Abstracts

Introduction: Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth. It is the most common congenital endocrine disorder. Neonatal screening test for hypothyroidism can allow its early detection. The course of disease can be permanent or transient. Some permanent congenital hypothyroidism has been linked to defects in proteins involved in the synthesis of thyroid hormones. One of the critical steps in the synthesis of thyroid hormone is the generation of H₂O₂ produced by dual oxidase at the apical membrane of follicular thyroid cells. This case report describes a permanent congenital hypothyroidism caused by compound heterozygous mutations in the DUOX2 gene.

Case: An 11-year-old-boy was born at 37 weeks of gestational age by Caesarean section. Birth weight was 2.8 kg. He was transferred to our hospital at 50 days of age due to abnormally low T₄ and high TSH in neonatal screening test. Thyroid function test revealed T₃ 77.8 ng/dl, free T₄ < 0.33 ng/dl, and TSH 38 uIU/ml. On physical examination, no major abnormality was found including goiter or neck mass. Thyroid sonography showed normally positioned thyroid gland with normal echogenicity. He has no family history of thyroid disease or autoimmune disease. He was diagnosed with congenital hypothyroidism and started taking levothyroxine 40 ug (11.1 ug/kg) daily. The boy has been regularly followed up in outpatient clinic until now. His language development was somewhat slower than peers until 3 years old, but showed normal development afterwards. Head circumstance and height were in the normal ranges. He has been adjusted the drug dosage based on weight and checked TFT every 3–4 months. The recent TFT showed T₃ 152 ng/dl, free T₄ 1.52 ng/dl, and TSH 8.29 uIU/ml with daily thyroid hormone replacement of 135 ug (1.98 ug/kg). The gene study for the evaluation of congenital hypothyroidism using diagnostic exome sequencing identified compound heterozygous mutations of the gene DUOX2. The sequences of DNA c.2444 Thymine and c.1462 Guanine were changed to Cytosine and Adenine. As a result, amino acid was changed from Leucine 815 to Proline and from Glycine 488 to Arginine.

Conclusion: We experienced a case of permanent congenital hypothyroidism with compound heterozygous mutations of DUOX2 gene inherited from the mother (c.2444T>C) and father (c.1462G>A).