Jordan Trishton Walker

Introduction

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Mitochondrial diseases are the most common group of genetic disorders, affecting mainly children and young adults. The mitochondrion is a highly specialized aerobic organelle that generates ATP via oxidative phosphorylation. Due to the defect in any of the mitochondrial proteins, the energy generated by oxidative metabolism has to be imported through a series of translocation processes. Therefore, the primary aim of clinical diagnosis is to diagnose mitochondrial disease patients by the specific phenotype of the patient\'s symptoms.[@b1-mjhid-10-1-e2018025] Unfortunately, the phenotypic presentations observed in mitochondrial disease patients often do not correlate with the specific enzyme defect nor with the underlying biochemical defects seen in the patient.

While the most common mitochondrial diseases are characterized clinically by a varied pattern of signs and symptoms, many patients have a clear molecular phenotype (i.e., mutation/in situ deletion). Clinical and pathologic heterogeneity can be found also in the different subtypes of the disorders.[@b2-mjhid-10-1-e2018025] Mitochondrial disease research aims to discover the structure and function of cells affected by the disorder, ideally by the gene targeted therapeutic intervention.

The term "genetic recessive" refers to a disease without other mutations in order to define the cause of the deficiency. In mitochondrial disorders, mtDNA mutations are often found in normal tissues, while they may be absent from the nuclear DNA. During the cloning of patients, identification of possible recombination events[@b3-mjhid-10-1-e2018025] or analysis of the various nuclear genome's characteristics (e.g. haplogroup) is necessary to affirm the causal relationship between the mutation and the disease. Whenever possible, the total amount of mtDNA analyzed should therefore be as high as possible, at least 5% of the total nuclear DNA.[@b4-mjhid-10-1-e2018025]

Patients with mtDNA mutations often exhibit a milder phenotype than patients carrying a normal nuclear genome. This fact has an impact on the biological mechanism, but is still difficult to treat.