背景:单羧酸转运蛋白8(MCT8)缺乏症是一种X连锁的隐性发育障碍,其特征是最初明显的躯干张力过低,后来的绝对姿态,以及由SLC16A2突变引起的严重智力障碍,SLC16A2负责将三碘甲状腺原氨酸(T3)转运到神经元中。我们对MCT8缺乏症患者进行了一项全国性调查,以澄清他们的现状。
方法:主要调查:2016-2017年,我们评估了1027家医院诊断为MCT8缺乏症的患者人数。二级调查:2017-2018年,我们向31家医院发送了病例调查(45例基因诊断),在初级调查中做出了回应。我们要求:1)围产期病史,2)发展史,3)头部MRI检查结果,4)神经生理学发现,5)甲状腺功能检查,5)基因检测结果。
结果:我们估计MCT8缺乏症的患病率为1,890,000中的1例,每百万出生的MCT8缺乏症的发生率为2.12(95%CI:0.99-3.25)。所有患者均表现为严重的精神运动性迟钝,没有人能够走路或说话。在我们的研究中发现的游离T3/游离T4(fT3/fT4)比率的显著更高的值可以是简单且有用的诊断生物标志物(我们的值11.60±4.14相对于对照3.03±0.38)。头颅MRI初始白质信号异常显示恢复,但是体感诱发电位(SEP)没有改善,这表明病人仍然功能失调。
结论:对于早期诊断,包括轻度病例,考虑临床过程可能很重要,早期头部MRI,SEP,和fT3/fT4比率。
BACKGROUND: Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked recessive developmental disorder characterized by initially marked truncal hypotonia, later athetotic posturing, and severe intellectual disability caused by mutations in SLC16A2, which is responsible for the transport of triiodothyronine (T3) into neurons. We conducted a nationwide survey of patients with MCT8 deficiency to clarify their current status.
METHODS: Primary survey: In 2016-2017, we assessed the number of patients diagnosed with MCT8 deficiency from 1027 hospitals. Secondary survey: in 2017-2018, we sent case surveys to 31 hospitals (45 cases of genetic diagnosis), who responded in the primary survey. We asked for: 1) perinatal history, 2) developmental history, 3) head MRI findings, 4) neurophysiological findings, 5) thyroid function tests, and 5) genetic test findings.
RESULTS: We estimated the prevalence of MCT8 deficiency to be 1 in 1,890,000 and the incidence of MCT8 deficiency per million births to be 2.12 (95 % CI: 0.99-3.25). All patients showed severe psychomotor retardation, and none were able to walk or speak. The significantly higher value of the free T3/free T4 (fT3/fT4) ratio found in our study can be a simple and useful diagnostic biomarker (Our value 11.60 ± 4.14 vs control 3.03 ± 0.38). Initial white matter signal abnormalities on head MRI showed recovery, but somatosensory evoked potentials (SEP) showed no improvement, suggesting that the patient remained dysfunctional.
CONCLUSIONS: For early diagnosis, including in mild cases, it might be important to consider the clinical course, early head MRI, SEP, and fT3/fT4 ratio.