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Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important since liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF.To determine the incidence of MLD in children under two with ALF and the utility of routine investigations to detect MLD.Thirty-nine consecutive infants with ALF were admitted to a single unit from 2009-11. All were extensively investigated using an established protocol. Genes implicated in MDS were sequenced in all cases and tissue mtDNA copy number measured where available.Five infants (17%) had genetically proven MLD: DGUOK (n = 2), POLG (n = 2) and MPV17 (1). Four of these died whilst one recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease following LT while five who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD.Low liver mtDNA copy number may be a secondary phenomenon in ALF.Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first two years of life.


Journal article


Journal of pediatric gastroenterology and nutrition

Publication Date



*Liver Unit †Clinical IMD ‡Radiology, Birmingham Children's Hospital, Birmingham §University of Birmingham, Birmingham ||Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust ¶Nuffield Department of Obstetrics and Gynaecology, University of Oxford #Wellcome Trust Centre for Mitochondrial Research and Highly Specialised Rare Mitochondrial Disease Service, Newcastle University **Genetics and Genomic Medicine, UCL Institute of Child Health, London, United Kingdom.