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Abstract: PO1619

Mitochondriopathy Manifesting as Inherited Tubulointerstitial Nephropathy Without Symptomatic Other Organ Involvement

Session Information

Category: Trainee Case Report

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Buglioni, Alessia, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Hasadsri, Linda, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Nasr, Samih H., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Hogan, Marie C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Moyer, Ann M., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Alexander, Mariam P., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Siddique, Khurrum, DHR Health, McAllen, Texas, United States
Introduction

Mitochondrial dysfunction has been previously described in cases of human chronic kidney disease (CKD), and subjects affected by primary systemic mitochondrial disease develop CKD. Importantly, examples of mitochondrially inherited tubulointerstitial kidney disease in subjects with no other symptomatic organ involvement have been recently reported, suggesting the possibility of a single-organ mitochondrial disease.

Case Description

A 12-year-old boy presented with short stature, low body weight, increased serum creatinine (1.9 mg/dL) and increased blood urea nitrogen (30 mg/dL). Blood analysis showed anemia, vitamin D deficiency, hyperparathyroidism and negative antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA). Ultrasound showed small kidneys (< 5th percentile). A kidney biopsy showed mild, non-specific, chronic tubulointerstitial nephropathy on light microscopy. Immunofluorescence was negative. Electron microscopy showed markedly enlarged and dysmorphic mitochondria. Given this striking histopathologic finding, genetic testing was performed. Next generation sequencing of mitochondrial DNA from the tissue biopsy showed the presence of a homoplasmic, single, missense mutation in position 616 (m.616T>C) of the mitochondrially encoded transfer RNA phenylalanine (MTTF) gene. Analysis of blood derived mtDNA from mother and maternal uncle, who were on dialysis since their 30s, confirmed the same homoplasmic mitochondrial mutation, supporting our hypothesis. The renal biopsy findings, genetic findings, and pattern of inheritance were strongly suggestive of a diagnosis of mitochondrially inherited tubulointerstitial kidney disease. Notably, no additional symptomatic organ involvement was present in these subjects.

Discussion

Our case supports and reinforces the possibility of a single organ-limited mitochondrial disease, regardless of the systemic mitochondrial DNA mutation status, potentially radically changing management and prognosis of these patients. Careful analysis of mitochondria by electron microscopy should be performed in patients with tubulointerstitial nephropathy and family history of kidney failure.