Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls

The assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become the most widely used procedure for the diagn osis of X-linked adrenoleukodystrophy (X-ALD) and other peroxisomal disorde rs. We present here out 17 years' experience with this assay. Three VLCFA p arameters, the level of hexacosanoic acid (C26:0), the ratio of C26:0 to te tracosanoic acid (C24:0), and of C26:0 to docosanoic acid (C22:0), were mea sured in 1,097 males (hemizygotes) with X-ALD, 1,282 women heterozygous for this disorder, including 379 obligate heterozygotes, 797 patients with oth er peroxisomal disorders, and 29,600 control subjects. All X-ALD hemizygote s who had not previously received Lorenzo's oil or a diet with a high eruci c acid content had increased VLCFA levels, but the application of a discrim inant function based on all three measurements is required to avoid the ser ious consequences of a false-negative result, VLCFA levels are increased at day of birth, thus providing the potential for neonatal mass screening, ar e identical in the childhood and adult forms, and do not change with age. E ighty-five percent of obligate heterozygotes had abnormally high VLCFA leve ls, but a normal result does not exclude carrier status. VLCFA levels were increased in all patients homozygous for Zellweger syndrome, neonatal adren oleukodystrophy, infantile Refsum's disease, and in patients with deficienc ies of peroxisomal acyl-coenzyme A oxidase, bifunctional enzyme, and 3-oxoa cyl-coenzyme A thiolase. In these patients the degree of VLCFA excess corre lated with clinical severity.