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Objectives: To identify asymptomatic boys with X-linked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression., Method: Eighty-nine boys (mean +/- SD baseline age, 4.7 +/- 4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities., Results: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. Abnormalities occurred only in the 64 patients who were aged 7 years or younger at the time therapy was started. There was significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. (For a 0.1-microg/mL increase in the length-adjusted area under the curve for the hexacosanoic acid level, the hazard ratio for incident MRI abnormalities in the whole group was 1.36; P = .01; 95% confidence interval, 1.07-1.72.) Results for patients aged 7 years or younger were similar (P = .04)., Conclusions: In this single-arm study, hexacosanoic acid reduction by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. We recommend Lorenzo's oil therapy in asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results.

The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy (AMN) in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. This study reports on 372 patients ranging in age from less than 3 years to adulthood, who have been followed at the Kennedy Krieger Institute. With the aim of determining whether a method could be developed to predict clinical course by analysis of data available at time of first contact, the patients were subdivided into 18 subgroups on the basis of age and the extent of brain magnetic resonance (MRI) abnormality utilizing the MRI scoring system devised by Loes et al. Scores to grade degree of neurologic and neuropsychologic impairment were also developed. There was strong correlation between MRI and the neurology and neuropsychology scores at baseline. Information based exclusively on age and MRI score at time of first contact was highly predictive of future clinical course and should aid the evaluation of the effects of bone marrow transplantation and the selection of patients for this procedure, as well as the evaluation of other therapies that may be developed in the future.