Endocrinology, Diabetes & Metabolism Case Reports (Jan 2022)
A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction
- Rikako Nakajima,
- Motohiro Sekiya,
- Yasuhisa Furuta,
- Takafumi Miyamoto,
- Masashi Sato,
- Kuniaki Fukuda,
- Keiichiro Hattori,
- Yasuhito Suehara,
- Mamiko Sakata-Yanagimoto,
- Shigeru Chiba,
- Yuka Okajima,
- Takashi Matsuzaka,
- Satoru Takase,
- Mikio Takanashi,
- Hiroaki Okazaki,
- Yusuke Takashima,
- Mikiko Yuhara,
- Yuta Mitani,
- Nako Matsumoto,
- Yuki Murayama,
- Mariko Ohyama Osawa,
- Nami Ohuchi,
- Daichi Yamazaki,
- Sayuri Mori,
- Yoko Sugano,
- Yoshinori Osaki,
- Hitoshi Iwasaki,
- Hiroaki Suzuki,
- Hitoshi Shimano
Affiliations
- Rikako Nakajima
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Motohiro Sekiya
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Yasuhisa Furuta
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Takafumi Miyamoto
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Masashi Sato
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba
- Kuniaki Fukuda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba; Department of Gastroenterology, Kasumigaura Medical Center, 2-7-14 Shimotakatsu, Tsuchiura, Ibaraki, Japan
- Keiichiro Hattori
- Department of Hematology, Faculty of Medicine, University of Tsukuba
- Yasuhito Suehara
- Department of Hematology, Faculty of Medicine, University of Tsukuba
- Mamiko Sakata-Yanagimoto
- Department of Hematology, Faculty of Medicine, University of Tsukuba
- Shigeru Chiba
- Department of Hematology, Faculty of Medicine, University of Tsukuba
- Yuka Okajima
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Takashi Matsuzaka
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan; Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Satoru Takase
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Bunkyo, Tokyo, Japan
- Mikio Takanashi
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Bunkyo, Tokyo, Japan
- Hiroaki Okazaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Bunkyo, Tokyo, Japan
- Yusuke Takashima
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Mikiko Yuhara
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Yuta Mitani
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Nako Matsumoto
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Yuki Murayama
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Mariko Ohyama Osawa
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Nami Ohuchi
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Daichi Yamazaki
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Sayuri Mori
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Yoko Sugano
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Yoshinori Osaki
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Hitoshi Iwasaki
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Hiroaki Suzuki
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- Hitoshi Shimano
- Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
- DOI
- https://doi.org/10.1530/EDM-22-0368
- Journal volume & issue
-
Vol. 1,
no. 1
pp. 1 – 7
Abstract
In this study, we herein describe a 47-year-old Japanese woman who manifested inheritable non-alcoholic steatohepatitis (NASH) and severe dyslipidemia. Interestingly, her NASH progression was ameliorated by treatment with a sodium– glucose co-transporter 2 (SGLT2) inhibitor. This inheritability prompted us to comprehensively decode her genomic information using whole-exome sequencing. We found the well-established I148M mutation in PNPLA3 as well as mutations in LGALS3 and PEMT for her NASH. Mutations in GCKR may contribute to both NASH and dyslipidemia. We further mined gene mutations potentially responsible for her manifestations that led to the identification of a novel M188fs mutation in MUL1 that may be causally associated with her mitochondrial dysfunction. Our case may provide some clues to better understand this spectrum of disease as well as the rationale for selecting medications.
