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.
Med Sci Monit
; 17(4): CR203-9, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21455106
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a Medicamentos
/
Esclerosis Cerebral Difusa de Schilder
/
Ácido Valproico
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ADN Polimerasa Dirigida por ADN
/
Epilepsia
/
Hígado
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Female
/
Humans
/
Infant
Idioma:
En
Revista:
Med Sci Monit
Asunto de la revista:
MEDICINA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Polonia