Novel deoxyguanosine kinase gene mutations and viral infection predispose apparently healthy children to fulminant liver failure.

摘要

Liver failure affects thousands of children each year and many cases have an unclear etiology (1). Mitochondrial disorders are a heterogeneous group of disorders (2) that are often suspected when a child develops chronic multisystemic disease. However, they are not often suspected in single-organ dysfunction or in acute illness. Mutations in the deoxyguanosine kinase (DGUOK) gene cause the hepatocerebral form of mitochondrial DNA (mtDNA) depletion syndrome (3), an autosomal recessive condition that has been described in individuals with hypotonia, nystagmus, developmental delay, progressive liver failure, and often early mortality (4,5). Given the limited number of cases reported, the clinical spectrum of this disorder and pathogenesis of acute clinical decompensation" remain unclear. In this article we show that liver dysfunction can manifest in otherwise normal twin males and we identify associated novel mutations in DGUOK. Importantly, we illustrate that a viral infection can trigger fulminant liver failure in the context of a genetic predisposition.