The role of DUOXA2 in the clinical diagnosis of paediatric congenital hypothyroidism.

Background: Congenital hypothyroidism (CH) is a common metabolic disorder in children that can impact growth and neurodevelopment, particularly during infancy and early childhood. DUOXA2, a DUOX maturation factor, plays a crucial role in the maturation and activation of dual oxidase DUOX2 (a member of the NADPH oxidase family). DUOX2 can correctly migrate to the plasma membrane from the endoplasmic reticulum (ER) with the help of DUOXA2, and the two proteins together form a stable complex that promotes hydrogen peroxide (H2O2) generation in the synthesis of thyroid hormones. Genetic alterations in DUOXA2 lead to defects function of DUOX2 protein causing inherited CH.

Objectives: This review discusses the relationship between DUOXA2 and CH, including the pathogenic mechanisms of CH in children caused by DUOXA2 mutations and the possibility or promise of DUOXA2 gene screening as a diagnostic marker for CH in the clinic.

Methods: The review synthesizes current research on the biological role of DUOXA2 and DUOX2 in thyroid hormone synthesis, the molecular impact of DUOXA2 mutations, and the clinical implications of genetic screening for CH.

Results: Mutations in DUOXA2 disrupt this process of H2O2 generation in the synthesis of thyroid hormones , leading to inherited CH. Early identification through DUOXA2 gene screening could improve diagnostic accuracy, which facilitates early intervention and personalized treatment.

Conclusions: DUOXA2 gene screening holds promise for enhancing diagnostic accuracy in CH. However, it cannot be used as a sole diagnostic indicator, and to optimize diagnostic sensitivity, it should be combined with the screening of other relevant genetic mutations and diagnostic tools. Further research is needed to refine screening protocols and explore therapeutic options.