Focal segmental glomerulosclerosis with a mutation in the mitochondrially encoded NADH dehydrogenase 5 gene: A case report

Tsukasa Naganuma; Toshiyuki Imasawa; Ikuo Nukui; Masakiyo Wakasugi; Hiroshi Kitamura; Yukiko Yatsuka; Yoshihito Kishita; Yasushi Okazaki; Kei Murayama; Yoshimi Jinguji

doi:10.1016/j.ymgmr.2023.100963

Focal segmental glomerulosclerosis with a mutation in the mitochondrially encoded NADH dehydrogenase 5 gene: A case report

Mol Genet Metab Rep. 2023 Mar 9:35:100963. doi: 10.1016/j.ymgmr.2023.100963. eCollection 2023 Jun.

Authors

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi 400-0027, Japan.
² Department of Nephrology, National Hospital Organization Chiba-Higashi National Hospital, 673 Nitona-cho, Chuoh-ku, Chiba-city, Chiba 206-8712, Japan.
³ Department of Clinical Pathology, National Hospital Organization Chiba-Higashi National Hospital, 673 Nitona-cho, Chuoh-ku, Chiba-city, Chiba 206-8712, Japan.
⁴ Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
⁵ Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
⁶ Center for Medical Genetics, Department of Metabolism, Chiba Children's Hospital, 579-1, Heta-cho, Midori-ku, Chiba 266-0007, Japan.

Abstract

NADH dehydrogenase 5 (ND5) is one of 44 subunits composed of Complex I in mitochondrial respiratory chain. Therefore, a mitochondrially encoded ND5 (MT-ND5) gene mutation causes mitochondrial oxidative phosphorylation (OXPHOS) disorder, resulting in the development of mitochondrial diseases. Focal segmental glomerulosclerosis (FSGS) which had podocytes filled with abnormal mitochondria is induced by mitochondrial diseases. An MT-ND5 mutation also causes FSGS. We herein report a Japanese woman who was found to have proteinuria and renal dysfunction in an annual health check-up at 29 years old. Because her proteinuria and renal dysfunction were persistent, she had a kidney biopsy at 33 years of age. The renal histology showed FSGS with podocytes filled with abnormal mitochondria. The podocytes also had foot process effacement and cytoplasmic vacuolization. In addition, the renal pathological findings showed granular swollen epithelial cells (GSECs) in tubular cells, age-inappropriately disarranged and irregularly sized vascular smooth muscle cells (AiDIVs), and red-coloured podocytes (ReCPos) by acidic dye. A genetic analysis using peripheral mononuclear blood cells and urine sediment cells detected the m.13513 G > A variant in the MT-ND5 gene. Therefore, this patient was diagnosed with FSGS due to an MT-ND5 gene mutation. Although this is not the first case report to show that an MT-ND5 gene mutation causes FSGS, this is the first to demonstrate podocyte injuries accompanied with accumulation of abnormal mitochondria in the cytoplasm.

Keywords: ATP, adenosine triphosphate; AiDIVs, age-inappropriately disarranged and irregularly sized vascular smooth muscle cells; COX IV, cytochrome c oxidase subunit 4; Case report; Cr, creatinine; FSGS, focal segmental glomerulosclerosis; Focal segmental glomerulosclerosis; GSECs, granular swollen epithelial cells; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MRC, mitochondrial respiratory chain; MT-ND5, mitochondrially encoded ND5; Mitochondrial nephropathy; NADH dehydrogenase 5; ND5, NADH dehydrogenase 5; OXPHOS:, oxidative phosphorylation; Podocyte; ReCPos, red-coloured podocytes; eGFR, estimated glomerular filtration rate; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; sCr, serum creatinine.

Publication types

Case Reports