Polyunsaturated fatty acid changes suggesting a new enzymatic defect in Zellweger Syndrome

The fatty acid composition of red blood cells, fibroblasts, forebrain, liver and kidney were studied in a 3-month-old infant who died from Zellweger Syndrome, and the results were compared with those of age-matched controls. Besides a typical increase in the very long chain fatty acids 26∶0 and 26∶1 and a great reduction in the plasmalogen levels, confirming the diagnosis of Zellweger Syndrome, some striking changes in the polyunsaturated fatty acid patterns were discovered. The most important was a very drastic decrease in the values of 22∶6ω3 and 22∶5ω6, the two products of Δ4-desaturation. In the kidney, the level of 22∶6ω3 fell below that of 26∶0. Consequently, the ratio 26∶0/22∶6ω3 (and 26∶1/22∶6ω3) was most useful in emphasizing the fatty acid anomalies, especially in renal tissue, where the 26∶0/22∶6ω3 ratio increased to almost 200 times the normal values. Other significant, although less consistent fatty acid alterations were increases in 18∶2ω6, 18∶3ω6, 20∶3ω6, 18∶4ω3 and 20∶4ω3, and a decrease in 20∶4ω6 in some tissues. The existence is proposed of a new enzyme defect in peroxisomal disorders, involving the desaturase system of long chain polyunsaturated fatty acids.