van den Bosch H, Schalkwijk C G, Schrakamp G, Wanders R J, Schutgens R B, Schram A W, Tager J M
Biochemistry Laboratory, Utrecht, The Netherlands.
Prog Clin Biol Res. 1988;282:139-50.
The Zellweger syndrome is a rare inborn error of metabolism characterized by the absence of morphologically distinguishable peroxisomes. As a consequence tissues and cells from Zellweger patients contain severely reduced levels of ether phospholipids. These are replaced by diacylphospholipids while keeping the polar headgroup composition of the cellular phospholipids constant. Both peroxisomal enzymes involved in glycero-ether lipid bond formation appear to be deficient. The experiments clearly establish that peroxisomes are indispensible for ether lipid biosynthesis. The peroxisomal deficiency in de novo ether lipid biosynthesis in fibroblasts and amniotic fluid cells can be applied in diagnostic assays. The mutation can be by-passed by feeding the cells with alkylglycerol. Similar characteristics as found for plasmalogen biosynthesis in Zellweger syndrome were assessed in other diseases with a general impairment of peroxisomal functions such as infantile Refsum disease and neonatal adrenoleukodystrophy as well as in rhizomelic chondrodysplasia punctata, a disease characterized by the absence of some, but not all, peroxisomal functions. Complementation analysis after somatic cell fusion has revealed that at least three genes must be involved in the biogenesis of fully functional peroxisomes.
泽韦格综合征是一种罕见的先天性代谢紊乱疾病，其特征是缺乏形态上可区分的过氧化物酶体。因此，泽韦格综合征患者的组织和细胞中醚磷脂水平严重降低。这些醚磷脂被二酰基磷脂取代，同时细胞磷脂的极性头部组成保持不变。参与甘油醚脂质键形成的两种过氧化物酶体酶似乎都存在缺陷。这些实验清楚地表明，过氧化物酶体对于醚脂质生物合成是不可或缺的。成纤维细胞和羊水细胞中从头合成醚脂质的过氧化物酶体缺陷可应用于诊断检测。通过用烷基甘油喂养细胞可以绕过该突变。在其他过氧化物酶体功能普遍受损的疾病中，如婴儿型雷夫叙姆病和新生儿肾上腺脑白质营养不良，以及在点状软骨发育不良（一种以部分而非全部过氧化物酶体功能缺失为特征的疾病）中，评估了与泽韦格综合征中缩醛磷脂生物合成相似的特征。体细胞融合后的互补分析表明，至少三个基因必须参与功能完全正常的过氧化物酶体的生物发生。
