Metabolic gene defects and risk of arrhythmia

Inherited single-gene disorders offer unique insights into the role of metabolic processes in arrhythmogenesis. Although many metabolic defects result in cardiomyopathy as a physiologic compensation, it is clear that specific perturbations are associated with particular arrhythmias. Metabolic gene defects may cause arrhythmia through many different pathways, including developmental effects on cardiac patterning, pathologic disruption of specific myocardial cell types, and the perturbation of several cellular processes. Understanding the precise pathways linking individual gene defects with discrete clinical arrhythmias will shed light, not only on monogenic disease, but also on common disorders such as ischemia or diabetes. Heart Metab. 2006;33:9–12.