Wide Spectrum of DUOX2 Deficiency: From Life-Threatening Compressive Goiter in Infancy to Lifelong Euthyroidism.
Wide Spectrum of DUOX2 Deficiency: From Life-Threatening Compressive Goiter in Infancy to Lifelong Euthyroidism.
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DOI：
10.1089/thy.2018.0461
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发表时间：
2019-07
期刊：
影响因子：
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通讯作者：
G. Dufort;S. Larrivée-Vanier;Dardye Eugène;X. De Deken;B. Seebauer;K. Heinimann;S. Lévesque;Serge Gravel;G. Szinnai;G. Van Vliet;J. Deladoëy
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作者：
G. Dufort;S. Larrivée-Vanier;Dardye Eugène;X. De Deken;B. Seebauer;K. Heinimann;S. Lévesque;Serge Gravel;G. Szinnai;G. Van Vliet;J. Deladoëy
6名患者被描述为具有双等位基因DUOX2变异和广泛变异的表型。患者1是一名婴儿，患有压迫性甲状腺功能减退性甲状腺肿，引起呼吸窘迫，经左旋甲状腺素(LT4)治疗后迅速缓解。他是DUOX2变异的复合杂合子，包括一个新的540个碱基对的缺失。患者2和3是兄弟姐妹，具有相同的DUOX2复合杂合子突变，但其中一例在14个月时出现明显的甲状腺功能减退，另一例终生正常。患者4是一个复合杂合子个体，患有轻度持续性先天性甲状腺功能减退症；他的妹妹(患者5)在新生儿筛查时仅有临界促甲状腺激素升高，这与纯合子DUOX2变异一致，对酶活性有轻微影响。他们的母亲甲状腺功能正常(患者6)是一个复合杂合子，与她的儿子有相同的DUOX2突变。靶向外显子测序没有发现任何相关的修饰物。结论是：(I)对于因甲状腺功能减退引起的呼吸窘迫的婴儿，及时进行LT4替代使不必要的手术；以及(Ii)DUOX2缺乏症的临床表现因个体和时间的不同而有很大差异，有理由定期重新评估LT4替代的必要性。
Six patients are described with bi-allelic DUOX2 variants and widely variable phenotypes. Patient 1 is an infant with a compressive hypothyroid goiter causing respiratory distress, which was promptly alleviated by levothyroxine (LT4). He was a compound heterozygote for DUOX2 variants, including a novel deletion of 540 base pairs. Patients 2 and 3 are siblings with the same compound heterozygous mutations of DUOX2, yet one had overt hypothyroidism at 14 months and the other lifelong euthyroidism. Patient 4 is a compound heterozygote individual and has mild persistent congenital hypothyroidism; his sister (patient 5) only had a borderline thyrotropin elevation at newborn screening, consistent with homozygous DUOX2 variants with a mild impact on enzyme activity. Their euthyroid mother (patient 6) is a compound heterozygote for the same DUOX2 mutations as her son. Targeted exome sequencing did not reveal any relevant modifiers. It is concluded that (i) prompt LT4 replacement in infants with respiratory distress due to a hypothyroid goiter makes surgery unnecessary; and (ii) the clinical expression of DUOX2 deficiency varies widely between individuals and over time, justifying periodic reevaluation of the need for LT4 replacement.