The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

Abstract

Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). The basic molecular mechanisms behind the role of infections in these conditions have not been completely clarified. This review points out the different mechanisms behind the relationship between IMDs and infections, providing an overview of this still-under-investigated area. Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. In addition, a dietary regimen with a reduced intake of both micro- and macronutrients can potentially compromise the ability of the immune system to deal with an infection. There is recent pre-clinical evidence showing that during infections there may be a disruption of substrates of various metabolic pathways, leading to further cellular metabolic alteration. Therefore, infective agents may affect cellular metabolic pathways, by mediation or not of an altered immune system. The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.

Keywords: acute metabolic decompensation; immune system; infection; inherited metabolic disorders; mitochondria.

Figure 1

The reciprocal interplay between infections and hereditary metabolic diseases—The metabolic alteration acting on the proper functioning of the immune system can be the cause of the infection and, in the case of IMDs at risk of AMD, also the cause of metabolic disruption. On the other hand, infection can directly affect the cellular metabolism, resulting in a perturbation of substrates, leading to a greater risk of metabolic disruption. Legend: MDs (mitochondrial diseases); OAs (organic acidurias); GSDs (glycogen storage diseases); CDGs (congenital glycosilation disorders); PKU (Phenylketonuria); UCDs (urea cycle disorders); FAODs (fatty acids oxidation disorders).