Acute liver failure with subsequent cirrhosis as the primary manifestation of TRMU mutations

• Published in: Journal of inherited metabolic disease Vol. 34; no. 1; pp. 197 - 201
• Main Authors: Schara, Ulrike, von Kleist-Retzow, Jürgen-Christoph, Lainka, Elke, Gerner, Patrick, Pyle, Angela, Smith, Paul M, Lochmüller, Hanns, Czermin, Birgit, Abicht, Angela, Holinski-Feder, Elke, Horvath, Rita
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01-02-2011; Springer Netherlands; Springer; Blackwell Publishing Ltd
• Subjects: Age; Base Sequence; Biochemistry; Biological and medical sciences; Child, Preschool; Cirrhosis; Electron transport; Enzymes; Female; Gastroenterology. Liver. Pancreas. Abdomen; Human Genetics; Humans; Infants; Internal Medicine; Liver Cirrhosis - diagnosis; Liver Cirrhosis - etiology; Liver Cirrhosis - genetics; Liver diseases; Liver Failure, Acute - complications; Liver Failure, Acute - diagnosis; Liver Failure, Acute - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mitochondria; Mitochondrial Diseases - complications; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - genetics; Mitochondrial DNA; Mitochondrial Proteins - genetics; Molecular Sequence Data; Mutation - physiology; Original Article; Other diseases. Semiology; Pediatrics; Point mutation; Skeletal muscle; Translation; tRNA Methyltransferases - genetics; Acute Liver Failure; Lactic Acidosis; Respiratory Chain Enzyme; Compound Heterozygous Mutation; CoQ10; Cirrhosis; Liver failure; Nutrition; Acute; Primary; Digestive diseases; Hepatic disease; Evolution; Genetics; Metabolic diseases; Mutation; Genetic disease
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-010-9250-z

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.