MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders

Abstract

Objective: We have found that docosahexaenoic acid (DHA; 22:6n-3), an important constituent of the CNS and retina, is dramatically decreased in patients with generalized peroxisomal disorders. Such a DHA deficiency could be pathogenic. Our aim was to test the possible beneficial effects of normalizing the DHA levels in these patients. The current report focuses on MRI changes during the treatment and reports follow-up evidence of myelin improvement in five peroxisomal disorder patients treated with DHA.

Methods: DHA ethyl ester (DHA-EE), about 90% pure, was used at daily oral doses of 100 to 600 mg. The treatment was monitored both clinically and biochemically, with periodic neurophysiologic and MRI examinations and repeated controls of liver tests and blood fatty acids by capillary column gas chromatography.

Results: DHA-EE normalized the blood levels of DHA in a few weeks. The levels of very-long-chain fatty acids decreased in plasma and those of plasmalogens increased in erythrocytes. Visual and liver function improved. On MRI, a virtual normalization of the brain myelin images was found in the three youngest patients. A clear improvement was noticed in the other two.

Conclusions: The beneficial effects obtained indicate that DHA deficiency plays an important role in the pathogenesis of peroxisomal disease, probably in relation to myelinogenesis. Early initiation of DHA therapy is thus strongly recommended in patients with generalized peroxisomal disorders.