We compared the formation of 14CO2 from [I-14C]fatty acids in homogenates of cultured skin fibroblasts and white blood cells from 25 patients with adrenoleukodystrophy (ALD) and from 24 controls. The ALD group included 16 boys with childhood ALD, five men with adrenomyeloneuropathy (AMN), and two boys and two girls with neonatal ALD. The substrates were unbranched saturated fatty acids ranging in chain length from 16-26 carbons. From C24:0, the radioactive CO2 production by homogenates of ALD fibroblasts and white blood cells was 17% and 37% of control, respectively, and from C26:0 it was 17% of control in ALD fibroblasts. The CO2 evolution from palmitate (C16:0) in the ALD was identical to the control group; for C18:0, the value for ALD cells was 76% of control, and fatty acids with chain lengths between C18:O and C24:0 gave intermediate results. Results for childhood ALD patients were similar to those for the AMN patients. More limited studies with cultured amniocytes of fetuses with childhood ALD gave results similar to those obtained with cultured skin fibroblasts, and results with neonatal ALD patients appeared to be the same as for childhood ALD and AMN. Studies of three women who were carriers for childhood ALD gave values intermediate between ALD and control. The total C26:0 levels in ALD cultured skin fibroblasts and white blood cells were 4-6 times that of control; the total C24:0 levels were increased 10-30%, whereas the C22:0 levels were unchanged. The results suggest that ALD patients have a defect in the oxidation of very long chain fatty acids (C24:0 and longer) but not for the degradation of fatty acids with a chain length of 18 carbons or less. Such a defect could account for the accumulation of the very long chain fatty acids in a variety of tissues and lipid moieties. The accumulation of these fatty acids, coupled with the metabolic data presented here, suggests that normal catabolism of very long chain fatty acids involves a metabolic pathway which is distinct from that for other fatty acids, and that this pathway is genetically deficient in patients with ALD.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health