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

  • Z. Grover
  • P. Lewindon
  • A. Clousten
  • A. Shaag
  • O. Elpeleg
  • D. ComanEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 21)


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.


Mitochondrial Respiratory Chain Copper Accumulation Acute Hepatic Failure Mitochondrial Oxidative Stress Menkes Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Professor Alex Kinsley (King’s College Hospital, London) for kindly reviewing the histopathological slides and Professor David Thorburn (MCRI, Melbourne) for performing the MRC studies.


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Z. Grover
    • 1
  • P. Lewindon
    • 1
    • 2
  • A. Clousten
    • 3
  • A. Shaag
    • 4
  • O. Elpeleg
    • 4
  • D. Coman
    • 2
    • 5
    • 6
    Email author
  1. 1.Department of GastroenterologyThe Lady Cilento Children’s HospitalBrisbaneAustralia
  2. 2.Department of Paediatrics and Child Health, School of MedicineThe University of QueenslandSt. LuciaAustralia
  3. 3.Department of Anatomical PathologyThe Royal Brisbane and Women’s HospitalBrisbaneAustralia
  4. 4.Metabolic Laboratory, Hadassah Medical CentreJerusalemIsrael
  5. 5.Department of Metabolic MedicineThe Lady Cilento Children’s HospitalBrisbaneAustralia
  6. 6.School of MedicineGriffith UniversityGold CoastAustralia

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