Background:    POLG (polymerase gamma) gene mutations lead to a variety of neurological disorders, including Alpers-Huttenlocher syndrome (AHS). The diagnostic triad of AHS is: resistant epilepsy, liver impairment triggered by sodium valproate (VA), and mitochondrial DNA depletion.
    Material/Methods:    A cohort of 28 children with mitochondrial encephalopathy and liver failure was qualified for retrospective study of mitochondrial DNA depletion and POLG mutations.
    Results:    The p.W748S POLG gene mutation was revealed in 2 children, the only ones in the cohort who fulfilled the AHS criteria. Depletion of mtDNA (16% of control value) was confirmed post mortem in available liver tissue and was not detected in the muscle. The disease started with drug-resistant seizures, failure to thrive and developmental regression at the ages of 7 and 18 months, respectively. Irreversible liver failure developed after VA administration. Co-existence of epilepsy, VA liver toxicity, lactic acidemia and muscle respiratory chain dysfunction led finally to the diagnosis of mitochondrial disorder (and AHS suspicion).
    Conclusions:    Our results confirm, for the first time, the occurrence of a pathology caused by POLG gene mutation(s) in the Polish population. POLG mutation screening and mtDNA depletion assessment should be included in differential diagnosis of drug-resistant epilepsy associated with a hepatopathy.

Keywords: Liver - pathology, Fatal Outcome, Epilepsy - enzymology, Drug Resistance, Diffuse Cerebral Sclerosis of Schilder - pathology, DNA-Directed DNA Polymerase - genetics, Child, Amino Acid Substitution - genetics, Mutation - genetics, Postmortem Changes, Spectrophotometry, Valproic Acid - therapeutic use