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Med Sci Monit. 2011 Apr;17(4):CR203-9.

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 gene.

Author information

  • 1Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute Warsaw, Poland. e.pronicka@czd.pl

Abstract

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.

PMID:
21455106
[PubMed - indexed for MEDLINE]
PMCID:
PMC3539522
Free PMC Article
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