The in-depth evaluation of suspected mitochondrial disease

Abstract

Mitochondrial disease confirmation and establishment of a specific molecular diagnosis requires extensive clinical and laboratory evaluation. Dual genome origins of mitochondrial disease, multiorgan system manifestations, and an ever increasing spectrum of recognized phenotypes represent the main diagnostic challenges. To overcome these obstacles, compiling information from a variety of diagnostic laboratory modalities can often provide sufficient evidence to establish an etiology. These include blood and tissue histochemical and analyte measurements, neuroimaging, provocative testing, enzymatic assays of tissue samples and cultured cells, as well as DNA analysis. As interpretation of results from these multifaceted investigations can become quite complex, the Diagnostic Committee of the Mitochondrial Medicine Society developed this review to provide an overview of currently available and emerging methodologies for the diagnosis of primary mitochondrial disease, primarily focusing on disorders characterized by impairment of oxidative phosphorylation. The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease.

Neuroimaging in Mitochondrial Disorders

“…As a group, they represent a challenge to clinicians, especially in children (ages, birth to 16 years), in whom clinical presentation and disease course show great variability [73].…”

Oxidative Therapy Against Cancer

“…CoQ also functions as an antioxidant that protects cells both by direct ROS scavenging and by regenerating other antioxidants such as vitamins C and E (Turunen et al, 2004). Given the critical role of CoQ in mitochondria function, it has been suggested that CoQ levels could be a useful biological marker of mitochondrial function (Haas et al, 2008). CoQ deficiency induces decreased mitochondrial respiratory enzymes activity, reduced expression of mitochondrial proteins involved in oxidative phosphorylation, decreased mitochondrial membrane potential, increased production of ROS, mitochondrial permeabilization, mitophagy of dysfunctional mitochondria, reduced growth rates and cell death (Rodriguez-Hernandez et al, 2009, Cotan et al, 2011.…”

A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant

“…In addition, a plasma alanine concentration of higher than 450 μmol/L was also indicative of mitochondrial disorder, reflecting chronic pyruvate accumulation. 5 Our patient first presented with isolated and persistent congenital hyperlactataemia. Screening for common mitochondrial DNA point mutations and large deletions at that time were all negative.…”