Plasmalogen biosynthesis in the diagnosis of peroxisomal disorders

Fibroblasts of patients suffering from peroxisomal disorders such as chondrodysplasia punctata (rhizomelic type), neonatal adrenoleukodystrophy, Zellweger syndrome and control fibroblasts were used for the evaluation of a procedure suitable for pre- and postnatal diagnosis. This technique is based on the detection of impaired peroxisomal plasmalogen synthesis by means of a double substrate, double labelling technique using 14C-labelled hexadecanol and 3H-labelled hexadecylglycerol as precursors for peroxisomal and microsomal plasmalogen synthesis. Pathological cells are characterized by a decreased utilization of hexadecanol, thus resulting in an increased 3H/14C ratio within plasmalogens. Sensitivity and reproducibility of this method were improved by changing both the chromatographic conditions and the calculation of the diagnostic parameters.