Renal Disease with Underlying Mitochondrial DNA Mutations in Three Patients Lacking Electron Microscopic Mitochondrial Morphologic Abnormalities
Larry N Cossey, Christopher P Larsen, Hugh D Massey, Timothy E Bunchman. University of Arkansas for Medical Sciences, Little Rock, AR; Nephropath, Little Rock, AR; Virginia Commonwealth University Medical Center, Richmond, VA
Background: Congenital mitochondrial DNA (mtDNA) mutations are a rare cause of disease, and are often heralded by renal manifestations. Renal findings reported in association with mtDNA gene mutations vary, including nephromegaly and cyst formation grossly. By light microscopy, focal segmental glomerulosclerosis (FSGS), tubulointerstitial nephritis, and glomerular hilar hyaline lesions can be seen. And, by electron microscopy mitochondrial changes including increased numbers of mitochondria, binucleate forms, variations in size, shape and internal substructure disorganization and cristae loss are identified.
Design: Three renal biopsy specimens from patients with underlying mtDNA mutations were identified from Virginia Commonwealth University Medical Center. All biopsies were studied by light, immunofluorescence, and electron microscopy.
Results: All patients were Caucasian; two males (brothers, ages two and six) and one female (15 months). Two patients underwent percutaneous kidney biopsy, while one (s/p heart transplant) underwent autopsy. All patients were hypertensive with tubular and glomerular-based proteinuria. One patient had increased lactate levels, two patients had nephromegaly on ultrasound, and all had associated polyuria and polydipsia with normal renal function. Renal biopsies revealed focal segmental glomerulosclerosis in two patients and chronic tubulointerstitial injury/fibrosis in all patients. Electron microscopy showed intact glomerular basement membranes of appropriate thickness for age with no podocytopathy or immune complex deposits. Focal mitochondrial alterations (enlargement with substructure autolysis) consistent with fixation artifact were identified in one patient. In the remaining two patients no mitochondrial abnormalities were identified.
Conclusions: mtDNA mutations are a rare cause of renal disease and are largely undefined. In previous case series, striking electron microscopic mitochondrial and podocyte morphological changes have been associated with these mutations and described in up to 100% of study participants. Here, we have presented three mtDNA mutation patients with clinical and light microscopic changes consistent with those previously published but lacking the ultrastructural mitochondrial abnormalities which are classically described.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 316, Monday Morning