（八）典型病例
先证者是一名12岁的巴西女孩，其父母身体健康、无血缘关系。患者正常产。在11岁时，由于甲状腺疾病到巴西利亚大学医院内分泌科就诊。追问病史，患者从11个月时起，血清TSH就轻微上升，同时T4升高、T3降低（表31-4）。该患者出生时体重较轻（2.45kg），头大、舌外伸、颅面部形态异常、双侧先天性趾侧弯。出生时没有做先天性甲状腺功能减退症的筛查。没有发现其他激素异常，血、尿氨基酸层析结果正常，血清的肌酸激酶和二磷酸果糖酶含量正常，其他先天性代谢疾病也被排除了。染色体组型为46，XX。患者出生后出现肌张力减退、体质虚弱、骨骼发育明显落后，她3岁8个月大时，骨骼年龄只有2岁。动作和智力发育也落后。2岁开始能走，3岁开始说话。6岁时，患者的循环IGF-1含量处在同龄、同性别孩子的正常值范围内。9岁时，神经肌电图检查和体感诱发电位实验确诊与腿部有关的双侧外周感觉神经异常。11岁时，患者身材矮小、体重超标、智力发育迟缓、双脚第五掌骨较短且不对称（右侧比左侧长1.5cm）、左眼睑轻度下垂、反射减退、脊柱后侧凸、颈部弯曲受限、腰部较弱。动作不协调、鸭子步态、Gowers征阳性。脑MRI正常。
表31-4 患者甲状腺指标的随访结果
注：11个月到8岁的结果是未用L-T3之前的情况；11岁的结果是应用L-T3治疗后的情况。
患者的血TSH在幼年期一直不正常，但甲状腺的形态正常、过氧化物酶抗体阴性。9岁时，患者接受了左甲状腺素（L-T4；Puran T4， Sanofi-Aventis，Sao Paulo， Brazil）的治疗，治疗剂量由3.4μg/（kg·d），逐渐上升到4.4μg/（kg·d）。之后，患者又用L-T3（Cytomel， King Pharmaceuticals， Bristol， TN）0.42μg/（kg·d）进行治疗。大剂量L-T4治疗能够抑制血清TSH水平，这说明患者T4到T3的转化过程受到了影响。口服L-T3逐渐使甲状腺激素达到正常水平，该治疗一直持续到现在。11岁时，患者进行了rT3的测定，其值升高，听力测试结果表明双侧听力感觉神经受损（右侧45dB、左侧40dB）。
基因测序，排除了DIO2基因突变。SBP2基因测序，发现患者存在杂合突变（R120X/R770X）。先证者从她父亲的基因中遗传了SBP2基因第3外显子的无义突变，这一突变导致终止密码子提前出现（R120X）。患者母亲的基因中包含第16外显子无义突变（R770X），这一突变遗传到了患者和她的妹妹身上。其他的16个亲属基因型都是R120X或R770X的杂合突变，这16位亲属都没有临床症状、血清TSH水平也正常。
患者的血浆GPx3活性显著下降（11U/G Hb，正常值为27.5～73.5 U/G Hb），而血清硒含量和SEPP水平都测不出（最低检测值分别是10μg/L、0.016mg/L）。患者的那些亲属的GPx3和硒的含量都在正常水平。
我们在L-T3的治疗基础上增加了口服富硒的酵母片（SelenoPrecise，Pharma Nord， Vejle， Denmark；200 g /d），在30天后，硒的水平上升到了58μg/L、GPx3活性也达到了正常范围内，然而SEPP的水平还是低于最低检测范围。在硒剂治疗2个月后，患者自行停用L-T3达21天，其TSH和FT4水平都有升高，但FT3却下降了。
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