Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γA

TLDR: Analysis of POLG1, the gene encoding the catalytic subunit of mitochondrial DNA polymerase, revealed that all the patients carried different allelic mutations in this gene, indicating that Alpers' syndrome is a major disease gene in mitochondrial disorders.

Abstract: We studied nine infant patients with a combination of progressive neurological and hepatic failure. Eight children, including two sibling pairs and four singletons, were affected by Alpers' hepatopathic poliodystrophy. A ninth baby patient suffered of a severe floppy infant syndrome associated with liver failure. Analysis of POLG1, the gene encoding the catalytic subunit of mitochondrial DNA polymerase, revealed that all the patients carried different allelic mutations in this gene. POLG1 is a major disease gene in mitochondrial disorders. Mutations in this gene can be associated with multiple deletions, depletion or point mutations of mitochondrial DNA (mtDNA). In turn, these different molecular phenotypes dictate an extremely heterogeneous spectrum of clinical outcomes, ranging from adult-onset progressive ophthalmoplegia to juvenile ataxic syndromes with epilepsy, to rapidly fatal hepatocerebral presentations, including Alpers' syndrome.