Simple diagnosis of the Zellweger syndrome by gas-liquid chromatography of dimethylacetals.

The absence of peroxisomes in patients with the cerebrohepatorenal syndrome of Zellweger leads to several biochemical abnormalities, including deficient synthesis of plasmalogens as well as accumulation of very long-chain fatty acids and intermediates in bile acid biosynthesis. Accumulation of very long-chain fatty acids in serum and fibroblasts has hitherto been used most extensively for diagnosis. Due to the relatively small amounts of the very long-chain fatty acids also in the Zellweger patients, and the risk for interfering impurities, such analyses are difficult. Direct assay of plasmalogens is also relatively difficult and time-consuming. In this report, we describe a relatively simple method for diagnosis, based on gas-liquid chromatography of a lipid extract of erythrocytes after methyl transesterification. The alpha, beta-unsaturated ether in the plasmalogen is converted to the dimethylacetal of the corresponding aldehyde, and the relative amount of plasmalogen is thus reflected by the ratio between 18:0 dimethylacetal and methyl stearate as well as by the ratio between 16:0 dimethylacetal and methyl palmitate. The ratio 18:0 dimethylacetal/methyl stearate was found to be 0.28 +/- 0.03 (mean +/- SD) after analyses of erythrocytes from healthy or non-Zellweger infants, but less than 0.02 in erythrocytes from three infants with the Zellweger syndrome. Preliminary work with amniotic fluid suggests that this analysis may be suitable also for prenatal diagnosis of the Zellweger syndrome.