Focal Segmental Glomerulosclerosis Due to A3243G Point Mutation in the mtDNA Coding for tRNALeu(UUR)

Mithocondropathies are inherited disorders that can result from abnormalities in the mitochondrial or nuclear DNA. Genetic abnormalities impacting the mitochondrial DNA (mtDNA) are consequently passed down through the maternal line. Renal manifestations of mtDNA disorders are often poorly recognized or misdiagnosed for the widely diverse phenotypic expression of this condition. Here we describe the case of a 34-year-old man with a history of chronic kidney disease, proteinuria, diabetes mellitus and sensorineural hearing loss, with worsening renal function and proteinuria with positive family history. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS) and whole exome sequencing revealed a mtDNA point mutation (A→G) at position 3243 which code for a transfer RNA (tRNALeu(UUR)). Different point mutations in mitochondrial DNA have now been associated with focal segmental glomerulosclerosis but genetic screening for mtDNA mutations is often neglected and this condition overlooked. Consideration of an underlying mitochondrial disease should be made in patients presenting with deafness, diabetes, renal failure and a positive family history of kidney disease.