背景:Allan-Herndon-Dudley综合征(MCT8缺乏症)是由编码单羧酸转运蛋白8(MCT8)的SLC16A2中的半合子致病变体引起的X连锁隐性病症。存在整体发育迟缓和神经功能缺损的患者,血清甲状腺功能检测异常.药物,3,3\',5三碘甲状腺素(TRIAC),最近被证明可以改善内分泌状况。诊断方法的改进是早期开始治疗的关键。
方法:我们描述了4例MCT8缺乏的中国患者经历不同的诊断异常。他们最初的表现包括全球发育迟缓和肌张力障碍。患者2也患有癫痫。患者1和2出现了两个新的变体:(1)半合子NM_006517.4(SLC16A2):c.11702T>A;p。(?),和(2)半合子NM_006517.4(SLC16A2):c.305dupT;p.(Val103GlyfsTer17)。患者3和4是具有半合子NM_006517.4(SLC16A2)的生物兄弟:c.305dupT;p。(Val103GlyfsTer17),这是2004年首次报道的。我们从患者1生命第1天收集的干燥血斑样品中获得了三碘甲状腺原氨酸(T3)和反向T3(rT3)的测量值,并研究了Iwayama等人提出的生物标志物(rT3和T3/rT3比率)。用于检测出生时的MCT8缺乏症。我们的数据证实,与健康新生儿相比,患者1的rT3水平显着降低,尽管检测到低T3水平和与对照组相当的T3/rT3比率。
结论:MCT8缺乏症患者常出现诊断异常。根据TSH和/或T4/fT4的生化测量,正常的新生儿甲状腺功能筛查结果可能会错过早期诊断。rT3的早期检测是改进当前诊断方法的关键。
结论:我们建议完整的甲状腺功能特征(TSH,T4/fT4,T3/fT3,rT3)对于所有出现无法解释的发育迟缓和/或肌张力障碍的儿科患者均应及早考虑。在新生儿筛查中可能包含rT3测量可能被证明是有希望的。
BACKGROUND: Allan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3\',5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment.
METHODS: We described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected.
CONCLUSIONS: Patients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach.
CONCLUSIONS: We recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising.