title: Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI.
abstract: Alpers syndrome is a fatal disorder due to mutations in the POLG gene encoding the catalytic subunit of mitochondrial DNA polymerase gamma (Pol gamma) involved in mitochondrial DNA (mtDNA) replication. We describe a case of Alpers syndrome due to POLG mutations, with rapidly progressive course, a fatal outcome, and an essentially normal brain MRI in the early oligo-symptomatic phase. Our observation suggests that Alpers syndrome should be considered even in patients with an initially unremarkable brain MRI. The patient was found to harbor the p.Q497H, p.W748S and p.E1143G mutations in cis on one allele, and a fourth mutation, the p.G848S on the other allele. Although the individual mutations detected in the presented case have been previously reported, the specific genotype formed by the particular combination of these is novel.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: N
authors.initials: N
authors.lastname: Brunetti-Pierri
authors.forename: K
authors.initials: K
authors.lastname: Selby
authors.forename: M
authors.initials: M
authors.lastname: O'Sullivan
authors.forename: G
authors.initials: G
authors.lastname: Hendson
authors.forename: C
authors.initials: C
authors.lastname: Truong
authors.forename: P J
authors.initials: PJ
authors.lastname: Waters
authors.forename: L-J
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human