Hepatic Copper Accumulation: A Novel Feature in Transient Infantile Liver Failure Due to TRMU Mutations?

Abstract

Defects in the mitochondrial respiratory chain can induce a heterogeneous range of clinical and biochemical manifestations. Hepatic involvement includes acute fulminant hepatic failure, microvesicular steatosis, neonatal non-alloimmune haemochromatosis and cirrhosis. Recently pathogenic mutations in tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) gene (OMIM 610230) have been demonstrated to cause transient infantile liver failure (OMIM 613070). The human TRMU gene encodes a mitochondrial protein, 5-methylaminomethyl-2-thiouridylate methyltransferase, whose molecular function is that of mitochondrial tRNA modification.We report an infant who presented with acute liver failure, in whom we observed hepatic copper intoxication and cirrhosis on liver biopsy. We postulate that the hepatic copper intoxication observed in our patient is most likely a secondary event associated with cholangiopathy. Periportal copper accumulation has been implicated in causing secondary mitochondrial dysfunction; the impact of copper accumulation in patients with TRMU mutations is unclear and warrants long-term clinical follow-up.Gut. 1980 Nov;21(11):970-6. (PMID: 7450563); JIMD Rep. 2013;11:117-23. (PMID: 23625533); Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):642-6. (PMID: 21996724); J Med Genet. 2011 Oct;48(10):660-8. (PMID: 21931168); Chem Biol Interact. 2006 Oct 27;163(1-2):77-85. (PMID: 16824500); Semin Liver Dis. 2007 Aug;27(3):259-73. (PMID: 17682973); J Nutr. 2003 May;133(5 Suppl 1):1527S-31S. (PMID: 12730458); J Inherit Metab Dis. 2011 Feb;34(1):197-201. (PMID: 21153446); Neurology. 2002 Nov 12;59(9):1406-11. (PMID: 12427892); Hum Mol Genet. 2011 Dec 1;20(23):4634-43. (PMID: 21890497); Front Biosci. 2007 Jan 01;12:1200-9. (PMID: 17127373); IUBMB Life. 2008 Jul;60(7):421-9. (PMID: 18459161); Am J Hum Genet. 2009 Sep;85(3):401-7. (PMID: 19732863); Arch Biochem Biophys. 2007 Jul 15;463(2):168-74. (PMID: 17382285); J Pathol. 1989 Jun;158(2):131-7. (PMID: 2754543); Semin Fetal Neonatal Med. 2011 Aug;16(4):222-8. (PMID: 21680270); EMBO J. 2004 Jan 14;23(1):244-54. (PMID: 14685266); Am J Clin Nutr. 2008 Sep;88(3):826S-9S. (PMID: 18779302); Mol Cell. 2006 Mar 17;21(6):775-85. (PMID: 16543147); Chang Gung Med J. 2009 Jul-Aug;32(4):346-53. (PMID: 19664341); J Gastroenterol Hepatol. 2002 Dec;17 Suppl 3:S403-7. (PMID: 12472971). Linking ISSN: 21928304. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2015 Feb 10. Current Imprints: Publication: 2019- : [Hoboken, NJ] : Wiley; Original Imprints: Publication: Berlin : SSIEM and Springer-Verlag, c2011. <br />