title: Alpers syndrome with mutations in POLG: clinical and investigative features.
abstract: Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder. Seventeen patients with Alpers syndrome or polymerase-γ gene mutations were identified. Case records of 12 patients with Alpers syndrome and polymerase-γ mutations in both alleles were reviewed. All patients manifested developmental delay or regression, refractory epilepsy, and biochemical liver dysfunction. Liver failure occurred in three patients previously treated with valproate. Other signs included ataxia, visual disturbance, motor paresis, and tremor. Myoclonic and focal motor seizures were common, often manifesting as status epilepticus. Electroencephalograms demonstrated absent/slow posterior dominant rhythms. Interictal discharges were common, usually involving the occipital lobes. Rhythmic high-amplitude delta with (poly)spikes was evident in four patients. Magnetic resonance imaging showed migratory, cortical, and subcortical T(2) hyperintensities in four children most often affected the parietal and occipital lobes. Developmental regression and refractory focal motor or myoclonic seizures are consistent clinical features of Alpers syndrome with polymerase-γ mutations. Liver dysfunction constitutes a late manifestation. Migratory T(2)/fluid attenuated inversion recovery signal abnormalities involving metabolically active occipital and sensorimotor cortical regions comprise characteristic imaging findings. Interictal and ictal electroencephalogram patterns are more variable than previously reported. Three common polymerase-γ mutations, in patients of European descent, can assist with rapid diagnosis, circumventing the need for liver biopsy.
authors: Genetic Health, Victorian Clinical Genetics Service, Melbourne, Victoria, Australia.
authors: Matthew F
authors: MF
authors: Hunter
authors: Heidi
authors: H
authors: Peters
authors: Renato
authors: R
authors: Salemi
authors: David
authors: D
authors: Thorburn
authors: Mark T
authors: MT
authors: Mackay
mesh_terms: D002648:Child; D002675:Child, Preschool; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D012640:Seizures / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human