Document Detail

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.
MedLine Citation:
PMID:  20138553     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures.
METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing.
RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome.
CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.
Russell P Saneto; Inn-Chi Lee; Mary Kay Koenig; Xinhua Bao; Shao-Wen Weng; Robert K Naviaux; Lee-Jun C Wong
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-06
Journal Detail:
Title:  Seizure     Volume:  19     ISSN:  1532-2688     ISO Abbreviation:  Seizure     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-08     Completed Date:  2010-06-14     Revised Date:  2014-10-21    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  England    
Other Details:
Languages:  eng     Pagination:  140-6     Citation Subset:  IM    
Copyright Information:
(c) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Anticonvulsants / adverse effects*
Child, Preschool
DNA Mutational Analysis
DNA-Directed DNA Polymerase / genetics*
Diffuse Cerebral Sclerosis of Schilder / drug therapy,  genetics,  physiopathology
Epilepsy / drug therapy,  genetics*,  physiopathology
Genetic Predisposition to Disease*
Liver Failure / chemically induced*
Magnetic Resonance Imaging
Valproic Acid / adverse effects*
Grant Support
Reg. No./Substance:
0/Anticonvulsants; 614OI1Z5WI/Valproic Acid; EC 2.7.7.-/POLG protein, human; EC DNA Polymerase

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