Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations
Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations
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DOI：
10.1007/s00431-006-0234-9
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Smeitink, Jan A. M.
中科院分区：
文献类型：
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作者：
de Vries, Maaike C.;Rodenburg, Richard J.;Smeitink, Jan A. M.
在8名儿童中，最常见的临床表现是发育迟缓、进食困难、各种形式的婴儿癫痫或精神运动发育迟缓和低眼压。患有复合氧化磷酸化酶复合体缺陷的儿童携带聚合酶伽马(POLGI)基因突变。8名患者中有5名在疾病过程中出现了严重的肝功能障碍。其中三名患者符合阿尔珀斯综合征的疾病标准。大多数儿童在肌肉中表现出呼吸链酶复合体I和III以及复合体II、复合体IV和/或PDHc的缺陷，而在成纤维细胞中检测到正常的酶活性。所有儿童都携带POLGI基因的纯合子或复合杂合子突变，其中包括两个与线粒体DNA耗尽相关的新突变。结论我们建议对合并肌肉氧化磷酸化缺陷的儿童进行POLGI突变分析，即使临床症状不是Alpers综合征。
Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or psychomotor developmental delay and hypotonia were the most frequent clinical disease presentations in eight.children with combined oxidative phosphorylation enzyme complex deficiencies carrying mutations in the polymerase gamma (POLGI) gene. Five out of eight patients developed severe liver dysfunction during the course of the disease. Three of these patients fulfilled the disease criteria for Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme complexes I and III, in combination with complex II, complex IV and/or PDHc in muscle, whereas in fibroblasts normal enzyme activities were measured. All children carried homozygous or compound heterozygous mutations in the POLGI gene, including two novel mutations in association with mtDNA depletion. Conclusion We suggest performing POLGI mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture is not Alpers syndrome.