Inborn errors of mitochondrial acyl-coenzyme a metabolism: acyl-CoA biology meets the clinic

Publication date: Available online 9 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Hao Yang, Chen Zhao, Marie-Christine Tang, Youlin Wang, Shu Pei Wang, Pierre Allard, Alexandra Furtos, Grant A. MitchellAbstractThe last decade saw major advances in understanding the metabolism of Coenzyme A (CoA) thioesters (acyl-CoAs) and related inborn errors (CoA metabolic diseases, CAMDs). For diagnosis, acylcarnitines and organic acids, both derived from acyl-CoAs, are excellent markers of most CAMDs. Clinically, each CAMD is unique but strikingly, three main patterns emerge: first, systemic decompensations with combinations of acidosis, ketosis, hypoglycemia, hyperammonemia and fatty liver; second, neurological episodes, particularly acute “stroke-like” episodes, often involving the basal ganglia but sometimes cerebral cortex, brainstem or optic nerves and third, especially in CAMDs of long chain fatty acyl-CoA metabolism, lipid myopathy, cardiomyopathy and arrhythmia. Some patients develop signs from more than one category. The pathophysiology of CAMDs is not precisely understood. Available data suggest that signs may result from CoA sequestration, toxicity and redistribution (CASTOR) in the mitochondrial matrix has been suggested to play a role. This predicts that most CAMDs cause deficiency of CoA, limiting mitochondrial energy production, and that toxic effects from the abnormal accumulation of acyl-CoAs and from extramitochondrial functions of acetyl-CoA may also ...

Source: Molecular Genetics and Metabolism - May 10, 2019 Category: Genetics & Stem Cells Source Type: research