@article {Uusimaa:June 2008:0013-9580:1038,
author = "Uusimaa, Johanna",
author = "Hinttala, Reetta",
author = "Rantala, Heikki",
author = "Paivarinta, Markku",
author = "Herva, Riitta",
author = "Roytta, Matias",
author = "Soini, Heidi",
author = "Moilanen, Jukka S.",
author = "Remes, Anne M.",
author = "Hassinen, Ilmo E.",
author = "Majamaa, Kari",
title = "Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus",
journal = "Epilepsia",
volume = "49",
year = "June 2008",
abstract = "Summary Purpose: Polymerase gamma (POLG) is the sole enzyme in the replication of mitochondrial DNA (mtDNA). Numerous mutations in the POLG1 gene have been detected recently in patients with various phenotypes including a classic infantile-onset Alpers-Huttenlocher syndrome (AHS). Here we studied the molecular etiology of juvenile-onset AHS manifesting with status epilepticus and liver disease in three teenagers. Patients and Methods: We examined 14- and 17-year-old female siblings (patients 1 and 2) and an unrelated 15-year-old girl (patient 3) with juvenile-onset AHS, sequenced POLG1, and the entire mtDNA, examined mtDNA deletions by amplification of the full-length mtDNA with the long PCR method and used real-time PCR to quantify mtDNA in the tissue samples. Results: The initial manifestations were migraine-like headache and epilepsy, and the terminal manifestations status epilepticus and hepatic failure. A homozygous W748S mutation in POLG1 was detected in the three patients. No deletions or pathogenic point mutations were found in mtDNA, but all three patients had mtDNA depletion. Conclusions: POLG mutations should be considered in cases of teenagers and young adults with a sudden onset of intractable seizures or status epilepticus, and acute liver failure. The W748S POLG1 mutation seems to lead to tissue-specific, partial mtDNA depletion in patients with juvenile-onset Alpers syndrome. Valproic acid should be avoided in the treatment of epileptic seizures in these patients.",
pages = "1038-1045(8)",
url = "http://www.ingentaconnect.com/content/bsc/epi/2008/00000049/00000006/art00012"
doi = "doi:10.1111/j.1528-1167.2008.01544.x"
}