MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNALeu(UUR). Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m2within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney.
Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria. Electronic address: michael.rudnicki@i-med.ac.at.
Michael
M
Rudnicki
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Johannes A
JA
Mayr
Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
Johannes
J
Zschocke
Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria.
Herwig
H
Antretter
Clinical Institute of Pathology, University of Vienna, Vienna, Austria.
Heinz
H
Regele
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
René G
RG
Feichtinger
Department of Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria.
Martin
M
Windpessl
Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria.
Gert
G
Mayer
Department of Internal Medicine III-Cardiology and Angiology, Medical University Innsbruck, Innsbruck, Austria.
Gerhard
G
Pölzl
D000328:Adult; D005198:Fanconi Syndrome; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000473:pathology; D017241:MELAS Syndrome / Q000150:complications* / Q000235:genetics; D008928:Mitochondria; D009154:Mutation; D011507:Proteinuria
Fanconi syndrome; Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome); focal segmental glomerulosclerosis (FSGS); heteroplasmy; kidney biopsy; proteinuria; renal