Journal of Inherited Metabolic Disease

, Volume 18, Supplement 1, pp 61–75 | Cite as

Polyunsaturated fatty acids in the developing human brain, erythrocytes and plasma in peroxisomal disease: therapeutic implications

  • M. Martinez


Patients with Zellweger syndrome and related peroxisomal disorders have profound changes in the polyunsaturated fatty acid (PUFA) patterns in brain and other tissues, with a constant decrease in docosahexaenoic acid (DHA, 22:6ω3) concentration. Arachidonic acid (AA, 20:4ω6) concentration is normal or increased and linoleic acid (LA, 18:2ω6) is increased in the brain of Zellweger patients. In the retina of these patients, the levels of DHA are extremely low. Since these alterations are reflected elsewhere, they can be detectedin vivo in patients with generalized peroxisomal disorders by measuring the PUFA content of plasma and erythrocytes, which show very low concentrations of DHA. The concentration of AA is low in plasma in generalized peroxisomal patients, although it is within normal limits in erythrocytes. Patients with X-linked adrenoleukodystrophy (X-ALD) or adrenomyeloneuropathy (AMN) have a normal DHA and AA content in both plasma and erythrocytes, unless they receive extremely low-PUFA diets.

Given the probable role of DHA deficiency in the pathogenesis of Zellweger syndrome (ZS), it is important to normalize concentrations of DHA, at least in blood, in an attempt to correct the DHA deficiency in brain. DHA ethyl ester was given orally to two infants with a peroxisome deficiency disorder for a year, and some favourable biochemical changes were produced in erythrocytes and plasma. Normalization of the DHA concentrations in erythrocytes was obtained in about 2 months, and the ratios 26:0/22:0 and 26:1/22:0 decreased markedly in plasma in the two patients. The plasmalogen ratio 18:0 dimethyl acetal/18:0 in erythrocytes increased to virtually normal values in both patients. There was a clear clinical improvement in the two patients, which paralleled the increase in blood DHA. The concentrations of AA and other PUFAs were closely monitored and, when necessary, AA was added to the diet. Such a DHA therapy, given under close biochemical and clinical control, and accompanied by a diet rich in other long-chain PUFA, is strongly recommended in all patients with peroxisomal disorders in whom a DHA deficiency is detected in blood.


Ethyl Ester Adrenoleukodystrophy Zellweger Syndrome Peroxisomal Disorder Peroxisomal Disease 
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Copyright information

© Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers 1995

Authors and Affiliations

  • M. Martinez
    • 1
  1. 1.Biomedical Research UnitAutonomous University of Barcelona, Maternity-Children HospitalBarcelonaSpain

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