Macroscopic characteristics of the native liver in children with MPV17‐related mitochondrial DNA depletion syndrome: an indication for performing liver transplantation?

2021 ◽  
Author(s):  
Mureo Kasahara ◽  
Seisuke Sakamoto ◽  
Akinari Fukuda ◽  
Reiko Horikawa ◽  
Reiko Ito ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mitochondrial Dna ◽  
Mitochondrial Dna Depletion ◽  
Native Liver ◽  
Mitochondrial Dna Depletion Syndrome

scholarly journals Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation

2020 ◽  
Author(s):  
Masaru Shimura ◽  
Naomi Kuranobu ◽  
Minako Ogawa-Tominaga ◽  
Nana Akiyama ◽  
Yohei Sugiyama ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mitochondrial Dna ◽  
Mitochondrial Diseases ◽  
Failure To Thrive ◽  
Neurological Complications ◽  
Mild Intellectual Disability ◽  
Initial Manifestation ◽  
Molecular Features ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome

Abstract Background Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan.Results We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 19 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T. Conclusions MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.

scholarly journals Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation

2020 ◽  
Author(s):  
Masaru Shimura ◽  
Naomi Kuranobu ◽  
Minako Ogawa-Tominaga ◽  
Nana Akiyama ◽  
Yohei Sugiyama ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mitochondrial Dna ◽  
Mitochondrial Diseases ◽  
Failure To Thrive ◽  
Neurological Complications ◽  
Mild Intellectual Disability ◽  
Initial Manifestation ◽  
Molecular Features ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome

Abstract BackgroundHepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate outcomes LT in MTDPS patients in Japan.ResultsWe retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 20 of 23 patients: MPV17 (n=13), DGUOK (n=4), POLG (n=1), MICOS13 (n=1), and TWNK (n=1). Eight MPV17-deficient patients harbored c.451dupC and all four DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n=13, 56.5%). The most frequent liver symptom was cholestasis (n=21, 91.3%). LT was performed on 11 patients, including eight MPV17-deficient and two DGUOK-deficient patients. Four patients, including one with mild intellectual disability, survived; seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T.ConclusionsMPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, but patients who had MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T and no marked neurologic manifestations before LT, had moderately better outcomes.

Hematopoiesis in the thymidine kinase 2 deficient mouse model of mitochondrial DNA depletion syndrome

2010 ◽  
Vol 33 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Xiaoshan Zhou ◽  
Magnus Johansson ◽  
Nicola Solaroli ◽  
Björn Rozell ◽  
Alf Grandien ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mouse Model ◽  
Thymidine Kinase ◽  
Deficient Mouse ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome ◽  
Thymidine Kinase 2

scholarly journals Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0203198 ◽  
Author(s):  
Kirsten E. Hoff ◽  
Karen L. DeBalsi ◽  
Maria J. Sanchez-Quintero ◽  
Matthew J. Longley ◽  
Michio Hirano ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome

My Name Was Charlie Gard

2017 ◽  
Vol 42 (11) ◽  
pp. 1-4
Author(s):  
Gerald D. Coleman ◽  
Keyword(s):  
Intensive Care Unit ◽  
Mitochondrial Dna ◽  
Intensive Care ◽  
Neonatal Intensive Care ◽  
Genetic Condition ◽  
Street Hospital ◽  
Great Ormond Street Hospital ◽  
Sufficient Energy ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome

My name was Charles Gard, but everyone called me Charlie. I was eleven months old when my parents decided to end a contentious legal fight and allow me to die. I was born in West London on August 4, 2016. My dad, Chris, is a postman and my mom’s name is Connie. They are still young, only in their thirties. At birth, I seemed to be developing normally, but by October, it was apparent that I was not gaining weight. I was then admitted to the neonatal intensive care unit at London’s Great Ormond Street Hospital, one of the world’s leading children’s hospitals, and treated for encephalomyopathic mitochondrial DNA depletion syndrome, a rare genetic condition which prevents cells from producing sufficient energy to maintain normal bodily functions. Experts on my form of MDDS, called RRM2B, unanimously agreed that there was no cure or treatment. At the time of my death on July 27, 2017, it was thought that only sixteen children globally have this condition.

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