CASE REPORT article
Front. Med.
Sec. Precision Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1562277
This article is part of the Research TopicThyroid hormones and dietView all 14 articles
Case Report: Mild and Complete Thyroid Peroxidase Deficiency in a Family with Literature Review
Provisionally accepted
- 1Dongguan Kanghua Hospital, Dongguan, China
- 2Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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Mild thyroid peroxidase (TPO) deficiency is an extremely rare autosomal recessive genetic disorder, with fewer than 10 cases reported globally. This condition is often misdiagnosed as primary hypothyroidism. We report a family with mild and complete TPO deficiency due to TPO gene mutations, including a novel mutation (p.R584W; c.1750T>G). The literature was reviewed to provide references for early clinical diagnosis and treatment. The proband was a 27-year-old man with a 20-year history of goiter and abnormal thyroid function. Thyroid function tests showed decreased thyroxine and free thyroxine levels, increased triiodothyronine and free triiodothyronine levels, elevated FT3/FT4 ratios, normal thyroid stimulating hormone levels, and elevated thyroglobulin levels. Ultrasound highlighted goiter with multiple nodules. Previous treatment with levothyroxine (L-T4) showed no improvement in goiter nor thyroid function, leading to discontinuation. Genetic sequencing revealed a heterozygous TPO gene mutation (p.R584W; c.1750T>G), predicted to be harmful by software including REVEL, PolyPhen2, and MutationTaster (REVEL score: 0.959). The proband's brother carried the same mutation albeit with different clinical manifestations, diagnosed as complete TPO deficiency. Moreover, the clinical characteristics and gene mutations of the nine previously reported cases of mild TPO deficiency were reviewed and summarized. Hence, this study reported a family with mild and complete TPO deficiency due to TPO gene mutations, and the literature was reviewed to enhance clinicians' understanding of the disease. Gene mutations aid in diagnosis. This is the first study to report the p.R584W; c.1750T>G gene mutation, enriching the gene pool for this rare disease. The efficacy of L-T4 treatment for mild TPO deficiency requires further observation and research.
Keywords: TPO gene mutation, mild TPO deficiency, Goiter, elevated FT3/FT4 ratio, Thyroglobulin
Received: 17 Jan 2025; Accepted: 30 May 2025.
Copyright: © 2025 Wu, Yan, Wu, Woo, Wu, Yan, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jin Zhang, Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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