01 April 2011
Drug-resistant epilepsia and fulminant valproate liver toxicity. Alpers-Huttenlocher syndrome in two children confirmed post mortem by identification of p.W748S mutation in POLG geneEwa PronickaADEFG, Anna Weglewska-JurkiewiczABCD, Maciej PronickiBC, Jolanta Sykut-CegielskaBD, Pawel KowalskiB, Magdalena PajdowskaBD, Irena JankowskaBD, Katarzyna KotulskaBD, Piotr KalicinskiB, Joanna Jakobkiewicz-BaneckaBCD, Grzegorz WegrzynADEF
Med Sci Monit 2011; 17(4): CR203-209
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
Most Viewed Current Articles
13 Apr 2020 : Original articleOutcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...
Med Sci Monit Basic Res 2020; 26:e920449
11 May 2020 : Original articleAnalysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...
Med Sci Monit Basic Res 2020; 26:e924085
05 Jan 2021 : Review articleA Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...
Med Sci Monit Basic Res 2021; 27:e929207
10 Aug 2020 : Clinical ResearchEffects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...
Med Sci Monit Basic Res 2020; 26:e925264