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

被引:29
作者
Pronicka, Ewa [6 ]
Weglewska-Jurkiewicz, Anna [1 ,6 ]
Pronicki, Maciej [2 ]
Sykut-Cegielska, Jolanta [6 ]
Kowalski, Pawel [3 ]
Pajdowska, Magdalena [4 ]
Jankowska, Irena [5 ]
Kotulska, Katarzyna [7 ]
Kalicinski, Piotr [8 ]
Jakobkiewicz-Banecka, Joanna [1 ]
Wegrzyn, Grzegorz [1 ]
机构
[1] Univ Gdansk, Dept Mol Biol, PL-80952 Gdansk, Poland
[2] CMHI, Dept Pathol, PL-04730 Warsaw, Poland
[3] CMHI, Dept Med Genet, PL-04730 Warsaw, Poland
[4] CMHI, Dept Biochem & Expt Med, PL-04730 Warsaw, Poland
[5] CMHI, Dept Gastroenterol, PL-04730 Warsaw, Poland
[6] CMHI, Dept Metab Dis Endocrinol & Diabetol, PL-04730 Warsaw, Poland
[7] CMHI, Dept Neurol & Epileptol, PL-04730 Warsaw, Poland
[8] CMHI, Dept Surg & Transplantol, PL-04730 Warsaw, Poland
来源
MEDICAL SCIENCE MONITOR | 2011年 / 17卷 / 04期
关键词
drug-resistant epilepsy; valproate liver toxicity; Alpers-Huttenlocher syndrome; POLG gene mutation; MITOCHONDRIAL-DNA POLYMERASE; ATAXIC NEUROPATHY; GAMMA; DISEASE; DEGENERATION; DEPLETION; CHILDHOOD; W748S; A467T;
D O I
10.12659/MSM.881716
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:CR203 / CR209
页数:7
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