Renal manifestations of genetic mitochondrial disease

Abstract

Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant variability in their clinical presentation and the broad spectrum of genes implicated in their etiology. These features contribute to the challenges of establishing a definitive diagnosis and understanding the pathogenetic mechanisms leading to kidney involvement in these diseases. Here, we review the deoxyribonucleic acid variants in the mitochondrial and nuclear genomes that have been associated with a kidney phenotype, and examine some of the possible pathogenic mechanisms that may contribute to the expression of a renal phenotype.

Mutations in mitochondrial DNA causing tubulointerstitial kidney disease

“…Mitochondrial tRNA Phe is one of two tRNAs that can form a structural component of the mitoribosome[18] which could exacerbate the translational defect. Although minor abnormalities in proximal tubular function are frequent in patients with other mitochondrial mutations, clinically overt renal disease is not usually observed[19]. Taken together with our study, these observations suggest that renal function is particularly susceptible to specific alterations in tRNA Phe .…”

Relatives in silent kidney disease screening (RISKS) study: A Chinese cohort study

“…This female predominance, along with familial clustering, may suggest maternal hereditary disorders, such as mitochondrial disease. In fact, renal dysfunction has been reported as the only manifestation and could be associated with point mutation or deletion of mitochondrial deoxyribonucleic acid (mtDNA) . Alternatively, there may be underdiagnosed kidney disease among index patients, such as lupus nephritis, which is female predominant.…”

Mitochondrial dysfunction in inherited renal disease and acute kidney injury

“…This mutation was initially described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a progressive neurodegenerative disorder that usually presents in children or young adults 94 . Approximately 80% of patients with MELAS syndrome harbour the mtDNA 3243 A>G mutation 95 , but other causative mtDNA mutations have also been reported 43 . The phenotypic expression of the mtDNA 3243 A>G mutation can be highly variable and causes a wide range of clinical manifestations, including muscle weakness, exercise intolerance, failure to thrive, developmental delay, progressive encephalopathy, migraine, stroke-like episodes, peripheral neuropathy and visual complaints due to ophthalmoplegia.…”