Renal involvement in mitochondrial cytopathies

Abstract

Mitochondrial cytopathies constitute a group of rare diseases that are characterized by their frequent multisystemic involvement, extreme variability of phenotype and complex genetics. In children, renal involvement is frequent and probably underestimated. The most frequent renal symptom is a tubular defect that, in most severe forms, corresponds to a complete De Toni-Debré-Fanconi syndrome. Incomplete proximal tubular defects and other tubular diseases have also been reported. In rare cases, patients present with chronic tubulo-interstitial nephritis or cystic renal diseases. Finally, a group of patients develop primarily a glomerular disease. These patients correspond to sporadic case reports or can be classified into two major defects, namely 3243 A>G tRNA(LEU) mutations and coenzyme Q10 biosynthesis defects. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this Educational Review, the principal characteristics of these diseases and the main diagnostic approaches are summarized.

Fig. 1

Coenzyme Q₁₀ and the electron flow in the respiratory chain. The figure depicts the central role of coenzyme Q₁₀ (CoQ₁₀) in shuttling electrons from complexs I and II to complex III. It is also an important cofactor for several mitochondrial dehydrogenases, such as dihydroorotate dehydrogenase (DHODH). The insert shows the structure of CoQ₁₀, which is comprised of a quinone group and a polyisoprenoid tail of different length, ranging from six isoprenyl subunits in yeast to ten subunits in humans. Respiratory chain complexes are detailed in Table 1

Fig. 2

Detection of cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activities in kidney cortex sections. Examples of abnormal histochemical staining in the renal cortex of three patients with a mitochondrial defect. a Uneven staining for COX and SDH in different tubular sections; b very low COX activity with normal SDH activity; c undetectable activity of both enzymes in tubular cells