X-LINKED ADRENOLEUKODYSTROPHY (ALD): HORMONAL AND CLINICAL FINDINGS DURING DIETARY ERUCIC-TRIOLEATE THERAPY

Abstract

X-linked ALD is characterized by primary adrenal insufficiency, demyelination and accumulation of very long chain fatty acids (VLCFA). VLCFA have a toxic effect on adrenocortical cell by increasing cell membrane microviccosity, leading to decreased ability to respond to ACTH (Whitcomb RW et al. J Clin invest 81:185·188, 1988). The regimen of VLCFA restricted diet supplemented with a mixture of oleic and erucic acid (GTEO) determined, for the first time, a normalisation of plasma VLCFA levels in ALD patients. Thus the data suggest that the pathological changes affecting the nervous and endocrine system may be delayed, or even arrested, in these patients. We now report the effects on the clinical course of ALD of this therapeutic approach in 18 patients treated with dietary-GTOE supplementation up to 5 years. There was no effect on the clinical course in patients with childhood and adolescent ALD assessed by neurological, neuropsycological, and neuroadiological (NMI) evaluations. Patients with adrenomyeloneropathy and presymptomic did not exhibit progression of the disease. All but 3 patients had hyposdrenalism. Plasma eldosterone levels were reduced and PRA was increased. Interestingly, normalisation of VLCFA levels in these patients resulted in an increase of aldosterone (M±SD: 112.3±94.6 vs 379.2±12.1 pg/ml, p<0.05) and a reduction of PRA levels form 10.2±7.6 to 5.1±2.8 ng/ml/h, confirming that VLCFA excess has a direct toxic effect on the adrenals whereas other factors are more likely involved in the determination of the pathological changes in the nervous system.