Allan-Herndon-Dudley综合征诊疗现状

Diagnosis and treatment of Allan-Herndon-Dudley syndrome

Allan-Herndon-Dudley综合征(AHDS)是因甲状腺激素(TH)转运体基因SLC16A2突变,致其编码单羧酸转运蛋白8(MCT8)功能失活,不能介导TH进入靶细胞引起的内分泌罕见病。主要临床表现为脑甲状腺功能减退(甲减)所致的严重神经运动发育异常,TH分泌代谢异常所致血清学(高T3、低T4、正常或轻度升高的促甲状腺激素)改变及外周组织甲状腺毒症。基因检测证实SLC16A2基因变异可确诊。有效的治疗应以改善脑甲减和外周甲状腺毒症以及恢复蛋白功能为目标。相比于激素替代治疗,T3类似物三碘甲状腺乙酸可以不依赖MCT8进入细胞,激活TH受体而发挥TH样作用,在改善患者外周甲状腺功能亢进症状上疗效显著,对神经表型可能也有效,是目前治疗AHDS较好的方法;旨在恢复MCT8功能的基因替代和伴侣分子治疗仍处于研究阶段。

Allan-Herndon-Dudley syndrome(AHDS)is a rare endocrine disorder caused by mutations in the thyroid hormone(TH)transporter gene SLC16A2,resulting in the inactivation of its encoded monocarboxylate transporter protein 8(MCT8),which fails to mediate the entry of TH into target cells.The main clinical manifestations are severe neuromotor developmental abnormalities due to cerebral hypothyroidism(hypothyroidism),serological changes(high T3,low T4,normal or mildly elevated thyroid stimulating hormone)due to abnormal secretory and metabolism of TH,as well as signs of thyrotoxicity in peripheral tissues.Confirmation of the SLC16A2 gene variant by genetic testing confirms the diagnosis.Effective treatment should aim to improve cerebral hypothyroidism and peripheral thyrotoxic and restore protein function.Compared with hormone replacement therapy,T3 analog Triac,which enters cells independent of MCT8 and activates TH receptors to exert thyromimetic actions,has been shown to be effective in improving patients′peripheral hyperthyroidism symptoms and may also be effective for the neural phenotype.Currently,it is a better treatment for AHDS.In addition,gene replacement and chaperone molecules aimed at restoring the transport function of MCT8 are still in the research phase.