Biochemical consequences in primary inborn errors of metabolism are often clear and predictable (i.e. elevated plasma phenylalanine in phenylalanine hydroxylase deficiency). However, potential biochemical consequences of genetic aberrations that do not have an obvious connection to metabolic pathways are much more difficult to understand.
Kohsaka et al. (PLOS One, 2014 9(11): 1-16) described cardiac mitochondrial abnormalities in a mouse model with cardiac targeted disruption of the circadian clock gene, Bmal1. These abnormalities include decreased expression of genes involved in fatty acid metabolism and the citric acid cycle, pathologic mitochondrial morphology, and defects in mitochondrial dynamics.
Such findings have implications for treatment approaches in disorders of circadian rhythm, and expand our understanding of the role of metabolism in complex phenotypes.
Hilary Vernon, MD PhD