Wu Xiaobi, Yan Yuerong, Wu Hongshi, Woo Kwan Leong, Wu Muchao, Yan Li, Li Yan, Zhang Jin
Department of Endocrinology and Metabolism, Dongguan Kanghua Hospital, Dongguan, China.
Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Front Med (Lausanne). 2025 Jul 1;12:1562277. doi: 10.3389/fmed.2025.1562277. eCollection 2025.
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 gene mutations, including a novel mutation (p.R584W; c.1750 T > 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 gene mutation (p.R584W; c.1750 T > 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 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.1750 T > 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.
轻度甲状腺过氧化物酶（TPO）缺乏症是一种极其罕见的常染色体隐性遗传病，全球报告的病例不足10例。这种疾病常被误诊为原发性甲状腺功能减退症。我们报告了一个因基因突变导致轻度和完全性TPO缺乏的家系，包括一个新的突变（p.R584W；c.1750 T>G）。对相关文献进行了综述，为早期临床诊断和治疗提供参考。先证者是一名27岁男性，有20年甲状腺肿和甲状腺功能异常病史。甲状腺功能检查显示甲状腺素和游离甲状腺素水平降低，三碘甲状腺原氨酸和游离三碘甲状腺原氨酸水平升高，FT3/FT4比值升高，促甲状腺激素水平正常，甲状腺球蛋白水平升高。超声检查显示甲状腺肿伴多个结节。先前使用左甲状腺素（L-T4）治疗对甲状腺肿和甲状腺功能均无改善，遂停药。基因测序发现一个杂合基因突变（p.R584W；c.1750 T>G），包括REVEL、PolyPhen2和MutationTaster在内的软件预测该突变有害（REVEL评分：0.959）。先证者的哥哥携带相同突变，临床表现不同，被诊断为完全性TPO缺乏症。此外，对先前报道的9例轻度TPO缺乏症病例的临床特征和基因突变进行了回顾和总结。因此，本研究报告了一个因基因突变导致轻度和完全性TPO缺乏的家系，并对相关文献进行了综述，以提高临床医生对该疾病的认识。基因突变有助于诊断。这是首次报道p.R584W；c.1750 T>G基因突变的研究，丰富了这种罕见疾病的基因库。L-T4治疗轻度TPO缺乏症的疗效需要进一步观察和研究。
