Ann Pediatr Endocrinol Metab.  2020 Mar;25(1):57-62. 10.6065/apem.2020.25.1.57.

Persistent goiter with congenital hypothyroidism due to mutation in DUOXA2 gene

• Jung SY
• Lee J
• Lee DH

• KMID: 2501039
• DOI: http://doi.org/10.6065/apem.2020.25.1.57

Abstract

Thyroid hormones are crucial for development of the central nervous system. Congenital hypothyroidism (CH) is the most common preventable disease resulting in mental retardation. A neonatal screening test (NST) can detect a mild form of CH that can be treated at an early age. Generally after 3 years of age, when most of the brain has matured, clinicians consider reevaluation of thyroid function for CH patients that have been identified with a normal thyroid gland at a normal position. This report presents three CH patients that developed normally, with persistent goiter despite thyroid hormone supplements. The patients’ initial thyroid-stimulating hormone (TSH) level after NST was 47, 157, and 57 mIU/L, respectively. Levothyroxine administration began at 1 or 2 months of age and was terminated after reevaluation at the age of 3, 15, and 5 years, respectively. However, 1 or 2 years later, they all resumed their medication due to increased TSH level coupled with newly developed or enlarged goiter. They all showed dual oxidase maturation factor 2 (DUOXA2) gene mutation: a homozygous mutation with DUOXA2 (c.413dupA; p.Tyr138*) in case 1, a presumed compound heterozygotic mutation with DUOXA2 (p.Tyr138*/p.Tyr246*) in case 2, and heterozygous mutations with DUOXA2 (c.738C>G; p.Tyr246*) and TPO (c.2268dupT; p.Glu757*) in case 3. When goiter persists or is newly developed despite a maintained euthyroid status, for those with transient CH history, follow-up to assess the thyroid function is recommended for at least 1 or 2 years, and genetic testing would be helpful. This study presents the first clinical cases of DUOXA2 mutation in Korea.

Keyword

Congenital hypothyroidism; Goiter; Genes

Figure

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  Fig. 1. (A) Case 1 developed a new goiter 1 year after stopping levothyroxine treatment. (B) Case 2 had a enlarged goiter 2 years after discontinuing levothyroxine. She still has the goiter despite a euthyroid state with taking levothyroxine. (C) Case 3 developed a new goiter 2 years after treatment cessation. All 3 patients resumed treatment and still have a goiter, while maintaining a euthyroid status.

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  Fig. 2. Next-generation sequencing for hypothyroidism revealed genetic mutations. (A) A homozygous mutation with DUOXA2 at c.413dupA (p.Tyr138*) was identified in case 1. (B) A presumed compound heterozygous mutation with DUOXA2 at c.413dupA (p.Tyr138*) (B-1) and c.738C>G (p.Tyr426*) (B-2) was identified in case 2. The mutation was assumed to be compound heterozygous based on her clinical presentation, although there was no confirmation as her parents refused to undergo genetic analysis. (C) Heterozygous mutations of both TPO at c.2268dupT (p.Glu757*) (C-1) and DUOXA2 at c.738C>G (p.Tyr246*) (C-2) were detected in case 3.

Reference

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