Science：氨基酸或有助治疗自闭症

Science发表的一篇研究论文称，一种普通的氨基酸膳食补充剂或可帮助治疗一种罕见的自闭症，这种自闭症伴有癫痫，由支链氨基酸的缺乏引起。

在分析了两个家族中患有自闭症和癫痫的儿童的基因组之后，这个国际研究团队发现患者的BCKD-kinase（Branched Chain Ketoacid Dehydrogenase Kinase）基因发生突变，加速了支链氨基酸（branched chain amino acids,BCAAs）的代谢。人体必需的支链氨基酸不能由人体自身合成，只能从食物中获取。由于基因突变，患者很快将摄入体内的这些必需支链氨基酸代谢掉，进而导致了自闭症的发生。

论文的合著者加利福尼亚大学的Joseph Gleeson说，"这一发现也令我们吃惊，而令人兴奋的是治疗方法也是如此简单，只需给予患者缺少的氨基酸即可。"

研究者首先用小鼠试验了氨基酸补充剂的效果，BCKD-kinase基因发生突变的小鼠表现出自闭症和癫痫的症状，这些症状在食用氨基酸补充剂后得到改善。随后研究者试图用补充剂改善自闭症患者体内氨基酸不平衡的状态，但尚无足够数据证明患者的症状确实得到改善。

大约有四分之一的自闭症患者伴有癫痫发作，但Gleeson说这种情况依然被认为是极其罕见的。研究者发现BCKD-kinase基因的突变将有助于自闭症和癫痫患者的诊断。

拓展阅读：                     

编译自Amino acids may help rare type of autism

doi:10.1126/science.1224631
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Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy

Gaia Novarino, Paul El-Fishawy, Hulya Kayserili, Nagwa A. Meguid, Eric M. Scott, Jana Schroth, Jennifer L. Silhavy, Majdi Kara, Rehab O. Khalil, Tawfeg Ben-Omran6, A. Gulhan Ercan-Sencicek, Adel F. Hashish, Stephan J. Sanders, Abha R. Gupta, Hebatalla S. Hashem, Dietrich Matern, Stacey Gabriel10, Larry Sweetman11, Yasmeen Rahimi1, Robert A. Harris1, Matthew W. State, Joseph G. Gleeson

Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1-α subunit of branched chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK mRNA and protein, E1-α phosphorylation, and plasma branched chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.