Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in childhood

Pediatr Nephrol. 2013 Mar;28(3):515-9. doi: 10.1007/s00467-012-2354-y. Epub 2012 Nov 8.


Background: We identified a mitochondrial tRNA mutation (m.586 G > A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance due to the absence of consistent reports of linkage to specific disease phenotypes and any data pertaining to its effects on mitochondrial function.

Case-diagnosis/treatment: A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency, and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with the need for peritoneal dialysis. Evaluation of her muscle and blood led to the identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G > A.

Conclusions: The m.586 G > A mutation is pathogenic and a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNA(Phe) and affects the translation of mitochondrial proteins and the stability of the electron transport chain.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cells, Cultured
  • DNA Mutational Analysis
  • Fatal Outcome
  • Female
  • Fibrosis
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / therapy
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / genetics
  • Mutation*
  • Oxygen Consumption / genetics
  • Peritoneal Dialysis
  • Phenotype
  • RNA / genetics*
  • RNA / metabolism
  • RNA Stability
  • RNA, Mitochondrial
  • RNA, Transfer, Phe / genetics*
  • RNA, Transfer, Phe / metabolism
  • Time Factors


  • Mitochondrial Proteins
  • RNA, Mitochondrial
  • RNA, Transfer, Phe
  • RNA