Mitochondrial DNA Analysis Should Be Considered in the Genetic Assessment of Focal Segmental Glomerulosclerosis or Unexplained Chronic Kidney Disease: A Case Report

Genetic testing is increasingly used to assist the precise diagnosis and clinical management of suspected genetic kidney diseases; however, mitochondrial DNA (mtDNA) analysis remains underutilized. Here we report a 61-year-old man who presented with chronic kidney disease (CKD), microscopic hematuria since childhood, bilateral sensorineural hearing loss (SNHL), and peripheral polyneuropathy. Laboratory reports showed serum creatinine 1.5 mg/dL with an estimated glomerular filtration rate of 55 mL/min/1.73m², no proteinuria, and a negative serological workup. Kidney biopsy demonstrated focal segmental glomerulosclerosis (FSGS) with segmental thinning of glomerular basement membrane and dysmorphic mitochondria. A 401 renal disease gene panel was negative, including type IV collagen genes. mtDNA analysis identified a pathogenic variant in the <i>MT-TV</i> gene (m.1642 G>A; NC_012920.1) with 2% heteroplasmy in leukocyte-derived DNA, confirmed in urine-derived DNA at 5% heteroplasmy. Genetic counseling was offered along with systemic evaluation revealing left ventricular hypertrophy on echocardiogram. The patient was started on levocarnitine and coenzyme Q10 with multidisciplinary care. This is the first reported case of FSGS with dysmorphic mitochondria and a pathogenic <i>MT-TV</i> variant confirmed via both leukocyte-derived and urine-derived DNA. It supports the role of mitochondrial dysfunction in CKD and highlights the importance of mtDNA analysis in the evaluation of FSGS and unexplained CKD.