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Acute infantile liver failure due to mutations in the TRMU gene.

ABSTRACT: 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.

SUBMITTER: Zeharia A

PROVIDER: S-EPMC2771591 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Acute infantile liver failure due to mutations in the TRMU gene.

Zeharia Avraham A Shaag Avraham A Pappo Orit O Mager-Heckel Anne-Marie AM Saada Ann A Beinat Marine M Karicheva Olga O Mandel Hanna H Ofek Noa N Segel Reeval R Marom Daphna D Rötig Agnes A Tarassov Ivan I Elpeleg Orly O

American journal of human genetics 20090901 3

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-methy ...[more]

PMID: 19732863

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