APPSPGHAN 2022

Kei Murayama

Director, Department of Metabolism, Chiba Children's Hospital

Japan

Research Areas:
Inherited Metabolic Diseases: Mitochondrial Disease, Lysosomal Disorder, Urea Cycle Disorders, Fatty Acid Oxidation Defects etc.

Professional Societies:
Membership:
The Japan Pediatric Society
The Japanese Society of Inherited Metabolic Disease, Board member, Vice Chairman
The Japanese Society of Mitochondrial Research and Medicine, Director
The Japanese Society of Pediatric Gastroenterology, Hepatology, and Nutrition, councilor
The Japanese Society for Mass-screening, councilor
The Japan Society of Human Genetics, councilor

Appointments Held:
Currently:
President, Center for Medical Genetics, Chiba Children’s Hospital,
Director, Department of Metabolism, Chiba Children's Hospital,
Chief, Chiba Cancer Center Research Institute
Visiting Professor, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University,
Visiting Professor, Department of Pediatrics, Graduate School of Medicine, Juntendo University,
Visiting Professor, Capital Medical University in Beijing and Beijing Children’s Hospital

Liver disease in mitochondrial disorders

Liver Symposium: Genetic and metabolic liver diseases

14 October 2022 (1030-1200) @ Sipadan Hall 2

“Mitochondrial disease” is a collective term used for various clinical disorders that are characterized by failure of mitochondrial function and energy production. Mitochondria are intracellular organelles enveloped by double membrane; they play an essential role in cells in the biosynthesis of adenosine triphosphate (ATP) via oxidative phosphorylation (OXPHOS). ATP is produced by the ATP-synthase complex, which is driven by the proton motive force created by the respiratory chain complexes (I, III, and IV). Impairment of OXPHOS may lead to organ damage. This dysfunction is referred to as mitochondrial disease, which occurs at a frequency of 1 in 5000 births in Japan and western countries.

Mitochondrial hepatopathy is one of the phenotypes of mitochondrial disease in children. Furthermore, mitochondrial DNA depletion syndrome (MTDPS) may occur owing to defects in the proteins involved in mitochondrial DNA (mtDNA) maintenance. This condition results in quantitative and qualitative defects within the mtDNA and is therefore classified as mtDNA maintenance defects. MTDPS has three clinical phenotypes: myopathic, encephalomyopathic, and hepatocerebral. Hepatocerebral MTDPS is known to cause acute liver failure during infancy and is associated with mutations in genes such as, DGUOK, MPV17, POLG, SUCLG1, and TWNK.

Transfer RNA maturation disorders are a growing group of genetic diseases associated with tissue-specific, and mostly neurological, phenotypes. However, some of them, including IARS1, LARS1, and TRMU, are strongly associated with liver phenotypes. Therefore, rapid genetic diagnosis may become important in near future, for early detection of these defects.

In this symposium, I focus on the clinical and genetic features, including mitochondrial medicine, of mitochondrial hepatopathy in children

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