The specific biochemical abnormality in adrenoleukodystrophy is the accumulation of very long-chain unbranched fatty acids, which are saturated or mono-unsaturated. The carbon lengths of these compounds are 24 to 30. They are found normally among the fatty acids of the cholesterol esters and gangliosides of the cerebral white matter and the adrenal cortex, and C26:0 makes up as much as five percent of the total fatty acids of cerebrosides and sulfatides of the normal brain [8,55–57]. Similarly, the VLCFA that accumulate in adrenoleukodystrophy are predominantly those with a chain length of 26. They are largely hexacosanoic acid (C26:0) (cerotic acid).Accumulation of these VLCFA has been demonstrated in cultured fibroblasts [14,57,58] and muscle cells [59,60]. In cultured fibroblasts, the ratio of C26 to C22 fatty acids has been useful in diagnosis, as well as the level of C26:0 [14]. The ratio was 0.76 in six patients with clinically typical disease and 0.78 in five patients with autopsy proven disease, while in controls it was 0.06. The concentrations of these same very long-chain saturated fatty acids in plasma are also increased [61], and this is the most convenient method for definitive diagnosis. The levels of C24 (lignoceric acid), C25 and C26 are significantly elevated, while those of C20 and C22 are normal. The C26:C22 ratios of hemizygotes are approximately five times those of controls. In general, the plasma assay is sufficient for diagnosis. In instances in which the data are equivocal, the fibroblast assay is employed. The accumulation of VLCFA in patients with adrenomyeloneuropathy is no different than in patients with classic adrenoleukodystrophy [14]. [treatment] The observation [94] that the addition of mono-unsaturated fatty acids such as oleic acid to cultured fibroblasts of patients leads to reduction in accumulation of VLCFA, led to the use of glyceryltrioleate in therapy. Glyceryltrierucate was even more effective in vitro [95], and this has led to the development of Lorenzo’s oil, a 4:1 mixture of trioleate and trierucate oils, named after the patient. Treatment does bring plasma levels of C26:0 to normal, but it is clear that the neurologic progression of the disease is not halted. Double blind placebo-controlled studies have not been done, but Lorenzo’s oil does not appear to be useful in patients who have demonstrated neurological regression [96,97].
[treatment] The observation [94] that the addition of mono-unsaturated fatty acids such as oleic acid to cultured fibroblasts of patients leads to reduction in accumulation of VLCFA, led to the use of glyceryltrioleate in therapy. Glyceryltrierucate was even more effective in vitro [95], and this has led to the development of Lorenzo’s oil, a 4:1 mixture of trioleate and trierucate oils, named after the patient. Treatment does bring plasma levels of C26:0 to normal, but it is clear that the neurologic progression of the disease is not halted. Double blind placebo-controlled studies have not been done, but Lorenzo’s oil does not appear to be useful in patients who have demonstrated neurological regression [96,97].