Division of Neurology, National Center for Child Health and Development, Japan; Department of Pediatrics, Shimada Ryoiku Medical Center for Challenged Children, Japan.
Department of Pediatrics, National Rehabilitation Center for Children with Disabilities, Japan.
Brain Dev. 2022 Nov;44(10):699-705. doi: 10.1016/j.braindev.2022.07.007. Epub 2022 Aug 6.
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.
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.
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.
For early diagnosis, including in mild cases, it might be important to consider the clinical course, early head MRI, SEP, and fT3/fT4 ratio.
单羧酸转运蛋白 8（MCT8）缺乏症是一种 X 连锁隐性发育障碍，其特征为最初明显的躯干张力减退，随后出现舞蹈手足徐动症姿势，以及严重的智力障碍，这是由于 SLC16A2 基因突变导致三碘甲状腺原氨酸（T3）无法进入神经元所致。我们开展了一项全国性的 MCT8 缺乏症患者调查，以明确其现状。
初步调查：2016-2017 年，我们评估了从 1027 家医院确诊的 MCT8 缺乏症患者数量。二次调查：2017-2018 年，我们向在初步调查中做出回应的 31 家医院（45 例遗传诊断）发送了病例调查。我们询问了：1）围产期病史，2）发育史，3）头部 MRI 结果，4）神经生理学结果，5）甲状腺功能检查，以及 5）基因检测结果。
我们估计 MCT8 缺乏症的患病率为 1/189 万，每百万新生儿中的发病率为 2.12（95%CI：0.99-3.25）。所有患者均表现出严重的精神运动发育迟缓，且均无法行走或说话。我们的研究中游离 T3/游离 T4（fT3/fT4）比值显著升高，这可能是一个简单且有用的诊断生物标志物（我们的比值为 11.60±4.14，而对照组为 3.03±0.38）。头部 MRI 上最初的白质信号异常显示恢复，但体感诱发电位（SEP）未见改善，表明患者仍存在功能障碍。
对于早期诊断，包括轻度病例，考虑临床病程、早期头部 MRI、SEP 和 fT3/fT4 比值可能很重要。
