Abnormal profiles of polyunsaturated fatty acids in the brain, liver, kidney and retina of patients with peroxisomal disorders.
The polyunsaturated fatty acid (PUFA) composition of the brain was studied in 8 patients with Zellweger's syndrome (ZS), 3 with neonatal adrenoleukodystrophy (NALD), one with bifunctional enzyme deficiency (BED), one with X-linked adrenoleukodystrophy (X-ALD), and one with adrenomyeloneuropathy (AMN). The PUFA composition of the liver, kidney and retina was studied in 8, 6 and 1 patients with ZS, respectively. An infant with NALD and a child with rhizomelic chondrodysplasia punctata (RCDP) were also studied for the PUFA composition of the liver. The liver and kidney of the patient with X-ALD and the liver of the patient with AMN were included in the study. The fatty acid values in the peroxisomal patients were compared with control data obtained in the normal developing brain (38 cases), liver (9 cases), kidney (7 cases) and retina (16 cases). The brain of a patient with metachromatic leukodystrophy (MLD) and the liver of a child with Krabbe's disease (KD) were also studied for comparison. The most constant and severe abnormality in all the peroxisomal patients was a drastic decrease in the total amount of docosahexaenoic acid (22:6 omega 3), especially in the brain. The other product of delta 4-desaturation, 22:5 omega 6, was generally decreased in the brain, liver and kidney of the ZS patients, but very much increased in the brain of two patients with NALD. The 22:6 omega 3/22:4 omega 6 ratio, which remains quite constant throughout normal brain development, was consistently decreased in the peroxisomal brain, in ZS as well as in NALD. This study confirms that, in classical Zellweger's syndrome, the two products of delta 4-desaturation are affected. In contrast, in neonatal adrenoleukodystrophy the deficiency is probably restricted to the omega 3 product of delta 4-desaturation, docosahexaenoic acid, especially in the brain, while the other product, 22:5 omega 6, is either normal or increased, perhaps in an attempt to compensate for the 22:6 omega 3 deficiency in brain membranes.
Martinez
M
M
Biomedical Research Unit, Maternity-Children Hospital, Ciudad Sanitaria Valle de Hebron, Barcelona, Spain.
D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D002806:Chondrodysplasia Punctata / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism; D012160:Retina / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D015211:Zellweger Syndrome / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated