Combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism which has been proposed being a benign condition. However, older patients may present with neurological manifestations such as seizures, memory problems, psychiatric problems and/ or cognitive decline. In fibroblasts from CMAMMA patients we have recently demonstrated a dysregulation of energy metabolism with increased dependency on β-oxidation for energy production. Because of the inability of the brain to rely efficiently on this pathway to retrieve the required energy to a great extent, we hypothesize an alternative disease-causing mechanism that does not only include the accumulation of the metabolites malonic and methylmalonic acids. Here, we suggest a novel hypothesis on the possible pathophysiological mechanism responsible for the development of neurological symptoms in the long-run.

中文翻译：

---

丙二酸和甲基丙二酸合并尿酸的脑代谢和神经系统症状。

丙二酸和甲基丙二酸合并尿酸症（CMAMMA）是先天性代谢错误，已经提出是良性疾病。但是，老年患者可能会出现神经系统表现，例如癫痫发作，记忆力问题，精神病和/或认知能力下降。最近，在来自CMAMMA患者的成纤维细胞中，我们证明了能量代谢的失调，并越来越依赖于β-氧化来产生能量。由于大脑无法有效地在很大程度上依赖该途径来获取所需的能量，因此，我们提出了一种替代性的致病机制，该机制不仅包括代谢产物丙二酸和甲基丙二酸的积累。这里，