Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pronicka, Ewa, Węglewska-Jurkiewicz, Anna, Pronicki, Maciej, Sykut-Cegielska, Jolanta, Kowalski, Paweł, Pajdowska, Magdalena, Jankowska, Irena, Kotulska, Katarzyna, Kaliciński, Piotr, Jakóbkiewicz-Banecka, Joanna, Węgrzyn, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539522/
https://www.ncbi.nlm.nih.gov/pubmed/21455106
http://dx.doi.org/10.12659/MSM.881716
Descripción
Sumario: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.