Abstract
Combined respiratory chain deficiency accounts for about 30% of mitochondrial respiratory chain deficiencies and is frequently associated with mtDNA depletion, deletions or point mutations. However combined respiratory chain deficiency may also be caused by mutations in nuclear genes affecting mitochondrial translation. Here we describe a 2-year-old girl, who developed an acute, isolated, severe liver failure with mitochondrial pathology and decreased respiratory chain enzyme activities both in liver and skeletal muscle at 4 months of age. Her liver function improved significantly within a month, liver function tests returned to normal. Liver cirrhosis remained without any further complications so far. Pathogenic compound heterozygous mutations were identified in the TRMU gene. This condition is one of the few mitochondrial disorders with a life-threatening onset showing recovery later in life, therefore a prompt diagnosis and treatment of these patients has great importance in clinical practice. We suggest that TRMU deficiency should be considered in infants with acute liver disease.
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Acknowledgements
We thank the patient and her family for contributing to this study. We want to thank S. Hertel and I. Kaus for excellent technical assistance, B. Leiendecker for critical reading the manuscript, Professor H. Baba (Dept. of Pathology, University of Essen) for the liver histology and Dr. P. Schneiderat and Professor T. Klopstock (Friedrich-Baur Institute, LMU, Munich) for the biochemical analysis.
RH is supported by the Newcastle upon Tyne Hospitals NHS Charity (RES0211/7262) and the Academy of Medical Sciences (UK, BH090164) and by the MRC (UK) as part of the MRC Centre for Neuromuscular Diseases. US and HL are part of the German network on muscular dystrophies (MD-NET) and JCvKR of the German network on mitochondrial disorders (mitoNET), respectively, both funded by the German ministry of education and research (BMBF, Bonn, Germany).
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Communicated by: Shamima Rahman
Competing interest: None declared.
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Schara, U., von Kleist-Retzow, JC., Lainka, E. et al. Acute liver failure with subsequent cirrhosis as the primary manifestation of TRMU mutations. J Inherit Metab Dis 34, 197–201 (2011). https://doi.org/10.1007/s10545-010-9250-z
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DOI: https://doi.org/10.1007/s10545-010-9250-z