The cerebro-hepato-renal (Zellweger) syndrome. Impaired de novo biosynthesis of plasmalogens in cultured skin fibroblasts.
In tissues of patients with the cerebro-hepato-renal (Zellweger) syndrome the plasmalogen content is very low. In order to study the biosynthesis of plasmalogens, skin fibroblasts of Zellweger patients, controls and heterozygotes, and amniotic fluid cells of controls were cultured in a medium supplemented with [1-14 C]hexadecanol or 1-O-[9,10-3H2]octadecylglycerol. The incorporation of 14C-label into the alkenyl moiety of plasmalogens was strongly reduced in Zellweger patients as compared to controls. The low concentration of 14C-labeled plasmalogens was not compensated for by an elevated levels of 14C-labeled alkyl phospholipids. Hexadecanol was partly oxidized to fatty acid in all cell lines and the incorporation of 14C-labeled fatty acid into phospholipids was comparable for patients and controls. [3H]Alkylglycerol was incorporated into plasmalogens with the same efficiency in Zellweger patients as in controls. These results indicate that only the reaction(s) involved in the introduction of the ether bond in the process of plasmalogen synthesis are deficient in Zellweger patients. The results also suggest that the hexadecanol incorporation patterns can be used for the (prenatal) diagnosis of the Zellweger syndrome.
D000653:Amniotic Fluid / Q000378:metabolism; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D005233:Fatty Alcohols / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D010955:Plasmalogens / Q000096:biosynthesis*; D011296:Prenatal Diagnosis; D012867:Skin / Q000378:metabolism*
D005233:Fatty Alcohols; D010743:Phospholipids; D010955:Plasmalogens; C005031:cetyl alcohol