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

TitleInfantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA.
Publication TypeJournal Article
Year of Publication2005
AuthorsFerrari, G, Lamantea, E, Donati, A, Filosto, M, Briem, E, Carrara, F, Parini, R, Simonati, A, Santer, R, Zeviani, M
JournalBrain
Volume128
IssuePt 4
Pagination723-31
Date Published2005 Apr
ISSN1460-2156
KeywordsBrain, Diffuse Cerebral Sclerosis of Schilder, Disease Progression, DNA Polymerase gamma, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Fatal Outcome, Female, Humans, Infant, Liver Failure, Magnetic Resonance Imaging, Male, Mutation
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.

DOI10.1093/brain/awh410
Alternate JournalBrain
Citation Key10.1093/brain/awh410
PubMed ID15689359
Grant ListGGP030039 / / Telethon / Italy