Orphanet Journal of Rare Diseases (Jan 2020)

Brain metabolism and neurological symptoms in combined malonic and methylmalonic aciduria

  • Sara Tucci

DOI
https://doi.org/10.1186/s13023-020-1299-7
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 3

Abstract

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Abstract 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.

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