Satoh Mari, Aso Keiko, Ogikubo Sayaka, Yoshizawa-Ogasawara Atsuko, Saji Tsutomu
J Pediatr Endocrinol Metab. 2015 May;28(5-6):657-61. doi: 10.1515/jpem-2014-0078.
Subjects who are heterozygous for thyroid stimulating hormone receptor (TSHR) gene mutations present various phenotypes that range from euthyroid to hyperthyrotropinemia. Similarly, heterozygous dual oxidase 2 (DUOX2) gene mutations result in variable phenotypes, such as transient congenital hypothyroidism, subclinical hyperthyrotropinemia, and euthyroid in children. Here, we describe an 8-year-old boy who had normal newborn screening results, but who developed nonautoimmune hypothyroidism at the age of 1 year and 8 months of age. He was heterozygous for previously reported R450H-TSHR mutation and heterozygous for a novel double mutant allele A1323T-DUOX2 and L1343F-DUOX2. He needed levothyroxine (l-T4) replacement therapy to keep serum TSH levels within normal limits; l-T4 dose of 2.01-2.65 μg/kg/day corresponded to the dose taken by children homozygous for R450H-TSHR and by children with permanent congenital hypothyroidism. Therefore, the coexistence of a heterozygous TSHR mutation and a heterozygous DUOX2 mutation may have affected the severity of his hypothyroid condition.
促甲状腺激素受体（TSHR）基因突变的杂合子患者表现出从甲状腺功能正常到促甲状腺激素血症等多种表型。同样，双氧化酶2（DUOX2）基因杂合突变也会导致不同的表型，如儿童期短暂性先天性甲状腺功能减退、亚临床促甲状腺激素血症和甲状腺功能正常。在此，我们描述一名8岁男孩，其新生儿筛查结果正常，但在1岁8个月时出现了非自身免疫性甲状腺功能减退。他是先前报道的R450H-TSHR突变的杂合子，也是新型双突变等位基因A1323T-DUOX2和L1343F-DUOX2的杂合子。他需要左甲状腺素（l-T4）替代治疗以维持血清TSH水平在正常范围内；2.01-2.65μg/kg/天的l-T4剂量与R450H-TSHR纯合子儿童和永久性先天性甲状腺功能减退儿童所服用的剂量相当。因此，TSHR杂合突变和DUOX2杂合突变的共存可能影响了他甲状腺功能减退的严重程度。
