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Umetsu et al. Hepatoma Res 2020;6:1 Hepatoma Research
DOI: 10.20517/2394-5079.2019.030

Case Report Open Access

First cases of MPV17 related mitochondrial DNA
depletion syndrome with compound heterozygous
mutations in p.R50Q/p.R50W: a case report

Shuichiro Umetsu , Ayano Inui , Sohya Kobayashi , Masaru Shimura , Tomoko Uehara , Hajime Uchida ,
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1
1
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Rie Irie , Tsuyoshi Sogo , Haruki Komatsu , Takako Yoshioka , Kei Murayama , Kenjiro Kosaki , Mureo
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Kasahara , Tomoo Fujisawa 1
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1 Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Kanagawa 230-0012, Japan.
2 Department of Metabolism, Chiba Children’s Hospital, Chiba 266-0007, Japan.
3 Center for Medical Genetics, Keio University School of Medicine, Tokyo 160-8582, Japan.
4 Department of Transplantation Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan.
5 Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan.
6 Department of Pediatrics, Toho University Sakura Medical Center, Chiba 285-8741, Japan.
7 Department of Pathology, National Center for Child Health and Development, Tokyo 157-8535, Japan.
Correspondence to: Shuichiro Umetsu, Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu
Hospital, 3-6-1, Shimosueyoshi, Tsurumi Ward, Yokohama, Kanagawa 230-0012, Japan. E-mail: s_umedu@tobu.saiseikai.or.jp
How to cite this article: Umetsu S, Inui A, Kobayashi S, Shimura M, Uehara T, Uchida H, Irie R, Sogo T, Komatsu H, Yoshioka T,
Murayama K, Kosaki K, Kasahara M, Fujisawa T. First cases of MPV17 related mitochondrial DNA depletion syndrome with compound
heterozygous mutations in p.R50Q/p.R50W: a case report. Hepatoma Res 2020;6:1.
http://dx.doi.org/10.20517/2394-5079.2019.030
Received: 13 Nov 2019 First Decision: 11 Dec 2019 Revised: 16 Dec 2019 Accepted: 24 Dec 2019 Published: 6 Jan 2020

Science Editor: Guang-Wen Cao Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Mutations in MPV17 lead to severe mitochondrial DNA depletion syndrome (MTDPS). All known p.R50W variants
in MPV17 are lethal. The homozygous variant p.R50Q in MPV17 among patients with Navajo neurohepatopathy
is known to allow longer survival, although heterozygous variants p.R50Q have not been reported. This is the first
clinical report in compound heterozygosity MPV17 mutation (p.R50W/p.R50Q). Three siblings were admitted
due to multiple hepatic nodules; none presented neurological abnormalities. However, they suffered from severe
hypoglycemia and cyclic vomiting. The diagnosis of MPV17-related MTDPS was confirmed by detection of a
compound heterozygous MPV17 mutation (p.R50W/p.R50Q), and striking reduction of hepatic mitochondrial
DNA. One patient developed pediatric-onset of hepatocellular carcinoma. Notably, all patients survived for
extended periods, including two patients who received liver transplantation, which contrasted the high mortality
rate associated with p.R50W mutations, as previously reported. The p.R50Q mutation might be associated with
longer survival and improved liver transplantation outcomes.

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