Restoring the DHA levels in the brains of Zellweger patients.
Patients with the Zellweger syndrome and its variants have very low levels of docosahexaenoic acid (DHA) in the brain, retina, and other tissues. Such a marked DHA deficiency could be related to the pathogenesis of peroxisomal disorders. Therefore, restoring the DHA levels in these patients can probably improve the clinical course of the disease. With this rationale, 20 patients with generalized peroxisomal disorders have been treated to date with DHA ethyl ester, at daily doses of 100-500 mg, for variable periods of time. Treatment has been always accompanied by a nutritious diet, normal for the age, in order to provide all the necessary nutrients and avoid a polyunsaturated fatty acid (PUFA) imbalance. The most constant improvement has been normalization of the DHA levels and liver function. Vision has improved in about half the patients and muscle tone has generally increased. Magnetic resonance imaging (MRI) examination revealed improvement of myelination in 9 patients. Significantly, the clinical improvement has been most marked in those patients who started the treatment before 6 mo of age. Biochemically, the plasma very long-chain fatty acids (VLCFA) 26:0 and 26:1n-9 decreased markedly despite the complete diet provided. In erythrocytes, the plasmalogen ratio 18: ODMA/18:0 increased in most cases, and sometimes even normalized. All these beneficial effects suggest that DHA deficiency plays a fundamental role in the pathogenesis of peroxisomal disease. Because DHA accretion is maximal during early brain development, it is essential to initiate the treatment as soon as possible. Otherwise, restoration of brain DHA levels and prevention of further damage will not be possible.
Martinez
M
M
Unit for Research in Biochemistry and Molecular Biology, Maternity-Children's Hospital Vall d'Hebron, Barcelona, Spain. mmr@hg.vhebron.es
D000326:Adrenoleukodystrophy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000367:Age Factors; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000517:prevention & control; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004910:Erythrocyte Membrane / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D020675:Peroxisomes / Q000378:metabolism; D010955:Plasmalogens / Q000378:metabolism; D011788:Quality of Life; D012035:Refsum Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D015211:Zellweger Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D008563:Membrane Lipids; D010955:Plasmalogens; D004281:Docosahexaenoic Acids; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester