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Focal segmental glomerulosclerosis associated with mitochondrial cytopathy
L M Doleris1, G S Hill, P Chedin
1Department of Internal Medicine and Nephrology, Hôpital A. Paré, Boulogne Billancourt, France. luc.moulonguet@apr.ap-hop-paris.fr
Background:
The nonspecific lesion of focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the disease depends on the degree of cellular dysfunction, and this correlates with the proportion of abnormal mitochondrial DNA in the cells and the dependence of tissues on oxidative metabolism. The most common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular diseases.
Methods:
Cases of four adult patients with FSGS and MC are reported. Routine histology and mitochondrial DNA analysis were carried out on renal biopsies.
Results:
Family history and clinical manifestations in the four patients with FSGS suggested a diagnosis of MC. An A3243G transition in the mitochondrial DNA tRNA(leu(UUR)) was found in lymphocytes and kidney. Glomerular lesions of FSGS were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles and small arteries.
Conclusion:
FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness.
Insights
Focal segmental glomerulosclerosis (FSGS) can be an early kidney manifestation of mitochondrial cytopathies (MCs). Researchers found a specific mitochondrial DNA mutation in patients, suggesting MCs should be considered in FSGS cases.
Area of Science:
- Nephrology
- Genetics
- Mitochondrial Diseases
Background:
- Focal segmental glomerulosclerosis (FSGS) is a nonspecific kidney lesion with varied causes.
- Mitochondrial cytopathies (MCs) involve cellular dysfunction due to abnormal mitochondrial DNA, impacting tissues reliant on oxidative metabolism.
- Renal manifestations of MCs primarily involve tubular dysfunction, with glomerular diseases being less commonly reported.
Observation:
- Four adult patients with FSGS and suspected MCs were studied.
- Renal biopsies underwent routine histology and mitochondrial DNA analysis.
- Clinical history and manifestations suggested MCs in patients with FSGS.
Findings:
- An A3243G transition in mitochondrial DNA tRNA(leu(UUR)) was identified in both lymphocytes and kidney tissue.
- FSGS lesions were accompanied by hyaline lesions, indicative of myocyte necrosis in afferent arterioles and small arteries.
- The findings link FSGS to mitochondrial DNA defects.
Implications:
- FSGS can be an early renal sign of MCs, potentially preceding other symptoms by years.
- Arteriolar lesions may cause glomerular hypertension and hyperperfusion, leading to secondary FSGS.
- MCs should be considered in idiopathic FSGS, especially with a family history of diabetes, neuromuscular disorders, or deafness.