Dietary erucic acid therapy for X-linked adrenoleukodystrophy.
We investigated the biochemical and clinical efficacy of dietary erucic acid (C22:1) therapy for X-linked adrenoleukodystrophy (ALD). In a double-blind crossover study of patients who were on chronic oleic acid (C18:1) therapy, addition of erucic acid to the diet led to a further reduction in plasma hexacosanoic acid (C26:0) concentration. We treated 12 newly diagnosed ALD patients with a diet enriched with erucic acid and oleic acid for 2 to 19 months. Mean plasma C26:0 concentration decreased to normal by 4 weeks, and the C26:0 composition of plasma sphingomyelin and phosphatidylcholine became normal by 4 months on therapy. Fatty acid analysis of postmortem tissues from 1 boy treated for 10 months suggested that dietary erucic acid entered the heart, liver, adrenal gland, and brain. Eight patients remained on treatment long enough (mean, 12 +/- 3 months) to evaluate their clinical response; 6 of these patients with moderate to advanced disease deteriorated neurologically or showed progression of white matter disease on brain magnetic resonance imaging whereas 2 mildly affected patients remained clinically stable after 10 and 19 months. No adverse effects of the diet occurred. We conclude that dietary erucic acid therapy is effective in lowering plasma C26:0 to normal in ALD patients, and may prevent further demyelination in some mildly affected boys.
Rizzo
W B
WB
Department of Pediatrics, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Leshner
R T
RT
Odone
A
A
Dammann
A L
AL
Craft
D A
DA
Jensen
M E
ME
Jennings
S S
SS
Davis
S
S
Jaitly
R
R
Sgro
J A
JA
D000326:Adrenoleukodystrophy / Q000178:diet therapy / Q000188:drug therapy / Q000235:genetics*; D002986:Clinical Trials as Topic; D004032:Diet; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D004883:Erucic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005227:Fatty Acids / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D008040:Genetic Linkage; D006801:Humans; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D019301:Oleic Acid; D009829:Oleic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D014960:X Chromosome
D004883:Erucic Acids; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D009829:Oleic Acids; C049811:erucic acid; D019301:Oleic Acid