Alpers Syndrome With Mutations in POLG: Clinical and Investigative Features

Genetic Health, Victorian Clinical Genetics Service, Melbourne, Victoria, Australia.
Pediatric Neurology (Impact Factor: 1.7). 11/2011; 45(5):311-8. DOI: 10.1016/j.pediatrneurol.2011.07.008
Source: PubMed


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.

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    • " patients , but only rarely in children , suggesting either that it develops later in the disease course , unless it simply reflects that electrophysio - logical investigations are not frequently performed in this age group . In support of our findings , peripheral neuropathy has not been reported in other series of children with POLG deficiency ( Hunter et al . , 2011 ; Isohanni et al . , 2011 ) . Ataxia was present in most of our cases ( 85% ) and was not a discriminating factor related to disease course or prognosis . Ataxia was largely related to the presence of severe sensory neuropathy , and all patients with sensory - axonal peripheral neuropathy had ataxia . The occa - sional occurrence of ata"
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