Cortès-Saladelafont E, Tristán-Noguero A, Artuch R, Altafaj X, Bayès A, García-Cazorla A
From the Laboratory of Synaptic Metabolism, ISCIII, Hospital Sant Joan de Déu, Barcelona, Spain; Department of Neurology, ISCIII, Hospital Sant Joan de Déu, Barcelona, Spain.
CIBERER, ISCIII, Hospital Sant Joan de Déu, Barcelona, Spain; Department of Molecular Biochemistry, Laboratory of Inborn Errors of Metabolism, Hospital Sant Joan de Déu, Barcelona, Spain.
Semin Pediatr Neurol. 2016 Nov;23(4):306-320. doi: 10.1016/j.spen.2016.11.005. Epub 2016 Nov 15.
The general concept of inborn error of metabolism is currently evolving into the interface between classical biochemistry and cellular biology. Basic neuroscience is providing increasing knowledge about the mechanisms of neurotransmission and novel related disorders are being described. There is a necessity of updating the classic concept of "inborn error of neurotransmitters (NT)" that considers mainly defects of synthesis and catabolism and transport of low weight NT molecules. Monogenic defects of the synaptic vesicle (SV), and especially those affecting the SV cycle are a potential new group of NT disorders since they end up in abnormal NT turnover and release. The most common clinical manifestations include epilepsy, intellectual disability, autism and movement disorders, and are in the continuum symptoms of synaptopathies. Interestingly, brain malformations and neurodegenerative conditions are also present within SV diseases. Metabolomics, proteomics, and other -omic techniques probably will provide biomarkers and contribute to therapeutic targets in the future.
代谢先天性缺陷的一般概念目前正朝着经典生物化学与细胞生物学的交叉领域发展。基础神经科学正在提供越来越多关于神经传递机制的知识，并且正在描述新的相关疾病。有必要更新“神经递质先天性缺陷（NT）”的经典概念，该概念主要考虑低分子量NT分子的合成、分解代谢和转运缺陷。突触小泡（SV）的单基因缺陷，尤其是那些影响SV循环的缺陷，是潜在的一组新的NT疾病，因为它们最终会导致NT周转和释放异常。最常见的临床表现包括癫痫、智力残疾、自闭症和运动障碍，并且属于突触病的连续症状。有趣的是，脑畸形和神经退行性疾病也存在于SV疾病中。代谢组学、蛋白质组学和其他“组学”技术可能会在未来提供生物标志物并有助于确定治疗靶点。
