Department of General Pediatrics and Adolescent Medicine, Laboratory of Clinical Biochemistry and Metabolism, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Mathildenstrasse 1, 79106, Freiburg, Germany.
Orphanet J Rare Dis. 2020 Jan 22;15(1):27. doi: 10.1186/s13023-020-1299-7.
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.
合并型丙二酸和甲基丙二酸尿症（CMAMMA）是一种代谢性疾病，曾被认为是良性疾病。然而，年长的患者可能会出现神经症状，如癫痫、记忆问题、精神问题和/或认知能力下降。在 CMAMMA 患者的成纤维细胞中，我们最近发现能量代谢失调，β-氧化对能量产生的依赖性增加。由于大脑不能有效地依赖这条途径来获取所需的能量，因此我们假设存在一种新的致病机制，不仅包括代谢产物丙二酸和甲基丙二酸的积累。在这里，我们提出了一个新的假设，即可能的病理生理机制负责长期发展中的神经症状。
