Sudden cardiac death in mitochondrial diseases

Abstract

Mitochondrial diseases (MD) constitute a heterogeneous group of genetic disorders that result from the dysfunction of the final common pathway of energy metabolism. The responsible mutation can be found in genes encoded in nuclear DNA or in mitochondrial DNA, causing differences in the clinical presentation and inheritance pattern. Most of these diseases have a multisystemic impact, mainly affecting tissues with a high oxidative energy requirement (heart muscle, skeletal muscle, and brain, for instance). Although death in DM is usually related to the clinical severity of the disease, sudden cardiac death (SCD) is possible also in patients with mild manifestations or even in asymptomatic individuals. This review aims to identify reported cases of SCD in MD (either diagnosed in life or at post mortem studies) and comprehensively analyze the macroscopic and microscopic pathological features described. There are only few documented cases (27), but the lack of notable cardiac phenotypic features in some cases, their low specificity, the scarce clinical personal and family information when the autopsy is performed and the little awareness of these diseases among doctors raise the suspicion that MD are infradiagnosed and many cases remain overlooked. Definitely, a correct diagnosis requires a high level of suspicion and a multidisciplinary approach with pathological and cardiological specialized tests both in the deceased proband and in the at-risk relatives to confirm or discard DM in order to tailor the follow-up, treatment and genetic counselling.