7501 T > A mitochondrial DNA variant in a patient with glomerulosclerosis

Abstract

The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported to be a specific change associated with mitochondrial cytopathy. However, at present, GSEC is not routinely evaluated. We, in this study, present a case of glomerulosclerosis, in which the presence of GSECs should provide us one clue to understand the pathogenesis of its progressive decline of renal function. A 54-year-old Japanese female, who had been diagnosed with Graves' disease, was referred for the examination and treatment of her proteinuria (5.4 g/gCre at the first visit to our hospital). A kidney biopsy showed 28.6% of the glomeruli to be globally sclerosed and 10.7% of the glomeruli to have completely collapsed. However, according to a light microscopic analysis, all other glomeruli showed an almost normal appearance, except for some slight enlargement. Almost 30% of the interstitium was damaged by fibrosis. Characteristically, GSECs were observed in the medulla collecting ducts. Although she had no symptoms of either myopathy or encephalopathy, no history of stroke-like episodes or difficulty in hearing, her serum concentrations of lactate and pyruvate were both elevated. Therefore, mitochondrial DNA sequencing was performed to assess the etiopathogenesis of her nephropathy. Consequently, a homoplasmic 7501 T > A replacement, which has not been previously reported in patients with renal diseases, was detected. This case suggests that the routine evaluation of GSECs can provide important clues to assess the etiopathogenesis of cryptogenic glomerulosclerosis.

Focal Segmental Glomerulosclerosis with a Mutation in the Mitochondrially Encoded NADH Dehydrogenase 5 Gene: A Case Report

“…Therefore, we emphasize the need to check for GSECs in cases of FSGS or glomerulosclerosis, especially in those with an unknown etiology. In addition, as COX IV is a subunit of Complex IV, COX IV staining can be used to stain mitochondria (27) and may help con rm the presence of abnormally increased numbers of mitochondria, as we previously reported (26,41). Furthermore, AiDIVs were observed in the arterioles and intralobular arteries in this case.…”

“…Interstitial brosis and tubular atrophy were observed in almost 30% of the area of the interstitium. Characteristically, granular swollen epithelial cells (GSECs), which have been reported as a speci c nding of mitochondrial diseases (25,26), were markedly observed in the distal tubular cells by AZAN staining (Fig. 1C).…”

Renal manifestations of primary mitochondrial disorders

“…In a consanguineous family with isolated COX-deficiency due to a mutation in the COX10 gene, which encodes the heme A:farnesyltransferase, increased urinary amino acids suggested proximal renal tubulopathy (65). In a 54-year-old female, the homoplasmic m.7501T>A mutation in the tRNA(Ser) gene manifested as proteinurea due to sclerosis of one-quarter of the glomeruli observed during kidney biopsy (66). Almost one-third of the interstitium was fibrotic in this patient.…”

“…Almost one-third of the interstitium was fibrotic in this patient. Tubular granular swollen epithelial cells (GSECs), which have been demonstrated to indicate a MID (67), were present in the medulla collecting ducts (66). In a study of six patients with encephalopathy, hepatopathy, and proximal tubulopathy, the causative mutation was detected in the BCS1L gene resulting in respiratory chain complex III deficiency (68).…”

Granular swollen epithelial cells in the kidney allograft: A clinicopathological study with special emphasis on possible marker for kidney allograft aging

“…Electron microscopy has demonstrated increased numbers of swollen mitochondria within GSECs, reflecting a granular appearance on light microscopy. The practical utility of GSEC has further been corroborated by a recent case report of a 54‐year‐old female patient lacking clinical features of mitochondrial disorders . In this case, histological findings of GSECs in the collecting ducts motivated further clinical examination.…”