The most important function of mitochondria in all tissues is oxidative phosphorylation namely the oxidation of fuel molecules by the respiratory chain and the concomitant energy transduction into ATP. A disorder of the respiratory chain results in a dramatic increase of reducing equivalents both in the mitochondria and cytoplasm. The general consequence of this is the increase of ketone body molar ratio (3-hydroxybutyrate/acetoacetate) and lactate/pyruvate molar ratio in plasma. The determination of these ratios is useful deciding whether enzymological studies of the respiratory chain are required. The observation of an abnormal oxidoreduction status in patients with Pearson marrow-pancreas syndrome led us to identify this disease as a mitochondrial cytopathy. Moreover, we were able to show that rearrangements of the mitochondrial genome are consistent features of this disease.