Kölker S, Sauer S W, Surtees R A H, Leonard J V
Department of General Paediatrics, Division of Inborn Metabolic Diseases, Universitatskinderklinik Heidelberg, Germany.
J Inherit Metab Dis. 2006 Dec;29(6):701-4; discussion 705-6. doi: 10.1007/s10545-006-0415-8. Epub 2006 Oct 14.
The blood-brain barrier (BBB) metabolically isolates the central nervous system (CNS) from the circulation and protects it against fluctuations of hydrophilic nutrients in plasma and from intoxication. Recent studies have shown that dicarboxylic acids (DCAs) are transported across the blood-brain barrier at very low rates. In organic acidaemias, neurological complications are common. We hypothesize that, as a result of the very limited efflux, in certain organic acidaemias there is pathological accumulation of DCAs (e.g. glutarate, 3-hydroxyglutarate, D-2- and L-2-hydroxyglutarate, methylmalonate) in the brain secondary to the metabolic block. At high concentrations some of these compounds may become neurotoxic. Treatment should be aimed at preventing the accumulation of these compounds using our understanding of the properties of the BBB.
血脑屏障（BBB）在代谢上使中枢神经系统（CNS）与循环系统隔离，并保护其免受血浆中亲水性营养物质波动及中毒的影响。最近的研究表明，二羧酸（DCAs）以非常低的速率穿过血脑屏障。在有机酸血症中，神经并发症很常见。我们推测，由于外流非常有限，在某些有机酸血症中，代谢阻滞会导致大脑中DCA（如戊二酸、3-羟基戊二酸、D-2-和L-2-羟基戊二酸、甲基丙二酸）病理性蓄积。在高浓度时，其中一些化合物可能会产生神经毒性。应利用我们对血脑屏障特性的了解，针对预防这些化合物的蓄积进行治疗。
