A new dietary therapy for adrenoleukodystrophy: Biochemical and preliminary clinical results in 36 patients

Abstract

A new dietary regimen has been administered for periods ranging from 60 days to 1 1/2 years in 34 patients with various forms of X-linked adrenoleukodystrophy (ALD), as well as in 1 patient with neonatal ALD and 1 patient with infantile Refsum's disease. The diet combines the administration of a glyceryl trioleate oil (GTO) with the dietary restriction of very-long-chain fatty acids (VLFA), particularly hexacosanoic acid (C26:0). Reductions in the levels of plasma C26:0 and other VLFA were achieved in 25 of the 36 patients. Fifteen of these 25 patients were treated for more than 100 days. The mean reduction of the plasma C26:0 level was 53% (range, 22 to 73%) in these 15 patients. While the focus of the study was on biochemical variables, comparison of pre- and post-diet studies of peripheral nerve function showed improvement in 1 patient with adrenomyeloneuropathy (AMN) and 1 heterozygote. In contrast, 2 patients with ALD onset in childhood developed new neurological deficits while on therapy. We conclude that it is possible to lower plasma VLFA levels in ALD patients. A clinical trial is indicated to test whether this approach can alter the neurological progression in patients with AMN or in symptomatic heterozygotes, and to determine whether it can prevent the onset of neurological disability in asymptomatic persons who have the biochemical defect of ALD.