Acute Infantile Liver Failure Due to Mutations in the TRMU Gene

Avraham Zeharia, Avraham Shaag, Orit Pappo, Anne Marie Mager-Heckel, Ann Saada, Marine Beinat, Olga Karicheva, Hanna Mandel, Noa Ofek, Reeval Segel, Daphna Marom, Agnes Rötig, Ivan Tarassov, Orly Elpeleg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Acute liver failure in infancy accompanied by lactic acidemia was previously shown to result from mtDNA depletion. We report on 13 unrelated infants who presented with acute liver failure and lactic acidemia with normal mtDNA content. Four died during the acute episodes, and the survivors never had a recurrence. The longest follow-up period was 14 years. Using homozygosity mapping, we identified mutations in the TRMU gene, which encodes a mitochondria-specific tRNA-modifying enzyme, tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase. Accordingly, the 2-thiouridylation levels of the mitochondrial tRNAs were markedly reduced. Given that sulfur is a TRMU substrate and its availability is limited during the neonatal period, we propose that there is a window of time whereby patients with TRMU mutations are at increased risk of developing liver failure.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - 11 Sep 2009
Externally publishedYes


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