Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases caused by mutations in either the mitochondrial or nuclear DNA. Glomerular diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS) associated with a new tRNA mutation site. A 34-year-old man with a history of living related kidney transplantation, diabetes, hearing loss, and developmental delay presented to the outpatient clinic with complaints of new behavioral difficulties, worsening symptoms, and brain involvement on imaging. Physical examination was remarkable for difficulty hearing, a pattern of dysarthric speech, and cerebellar gait. Laboratory investigations including lactate levels were unremarkable. Based on this set of clinical circumstances, concern for an underlying genetic abnormality was raised. Multiple metabolic tests were unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change at position m.5538G>A. Genotype-phenotype correlations are consistent with this tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is the first case describing FSGS-associated MD caused by an m.5538 G>A mutation. Consideration of an underlying MD should be made in patients presenting with deafness, neurologic changes, diabetes, and renal failure.
Keywords: deafness; focal segmental glomerulosclerosis (FSGS); hearing loss; kidney transplantation; mitochondrial disease; whole exome sequencing.