期刊
MEDICAL SCIENCE MONITOR
卷 17, 期 4, 页码 CR203-CR209出版社
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/MSM.881716
关键词
drug-resistant epilepsy; valproate liver toxicity; Alpers-Huttenlocher syndrome; POLG gene mutation
资金
- CMHI [119/09]
- Polish Mitochondrial Network
- [PB 0890/P05/2005/29]
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.
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