Zellweger syndrome: Biochemical procedures in diagnosis, prevention and treatment
- 128 Downloads
In patients with cerebro-hepato-renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes in which peroxisomes are normally involved. These include the catabolism of very long chain (>C22) fatty acids, the biosynthesis of ether-phospholipids and of bile acids, the catabolism of phytanic acid and the catabolism of pipecolic acid. Many diagnostic tests for Zellweger syndrome have become available in recent years. In classic Zellweger syndrome abnormal C27-bile acids, very long chain fatty acids, dicarboxylic acids and pipecolic acid accumulate in the plasma of the patients. Moreover, depending upon the diet, plasma phytanic acid concentrations may be elevated. In platelets the activity of acyl-CoA: dihydroxyacetone phosphate acyltransferase is deficient; in erythrocytes from young (<4 months) patients the plasmalogen content of the phospholipids is decreased.
In cultured fibroblasts from skin and from chorionic villus and cultured amniotic fluid cells from Zellweger patients the plasmalogen level is lowered; there is a decreased activity of acyl-CoA: dihydroxyacetone phosphate acyltransferase, alkyl dihydroxyacetonephosphate synthase and phytanic acid oxidase; thede novo biosynthesis of plasmalogens and the peroxisomal β-oxidation of fatty acids are impaired and the intracellular localization of catalase is abnormal.
Dietary treatment of patients with Zellweger syndrome has not so far resulted in an objective clinical improvement. As Zellweger syndrome is usually fatal in early life, prenatal diagnosis of the disease is important.
KeywordsDicarboxylic Acid Phytanic Acid Acid Oxidase Dihydroxyacetone Phosphate Pipecolic Acid
Unable to display preview. Download preview PDF.
- Borst, P. Animal peroxisomes (microbodies), lipid biosynthesis and the Zellweger syndrome.Trends Biol. Sci. 8 (1983) 269–272Google Scholar
- Farrell, K., Dimmick, J. E., Applegarth, D. A., Wong, L. E., Tze, W. J., McCormick, A. Q., Jan, J. E. and Moser, H. W. Peroxisomal abnormalities in neonatal adrenoleukodystrophy.Ann. Neurol. 14 (1983) 379Google Scholar
- Goldfischer, S., Moore, C. L., Johnson, A. B.et al. Peroxisomal and mitochondrial defects in the cerebrohepatorenal syndrome.Science 132 (1973) 62–64Google Scholar
- Heymans, H. S. A. Cerebro-hepato-renal (Zellweger) syndrome. Clinical and biochemical consequences of peroxisomal dysfunction. PhD Thesis. University of Amsterdam (1984)Google Scholar
- Kelley, R. I. Review: the cerebro-hepato-renal syndrome of Zellweger, morphologic and metabolic aspects.Am. J. Genet. 16 (1983) 503–517Google Scholar
- Mannaerts, G. P., Debeer, L. J., Thomas, J. and de Schepper, P. J. Mitochondrial and peroxisomal fatty acid oxidation in rat liver homogenates and isolated hepatocytes from control and clofibrate-treated rats.J. Biol. Chem. 245 (1979) 4585–4595Google Scholar
- Schutgens, R. B. H., Romeijn, G. J., Wanders, R. J. A., van den Bosch, H., Schrakamp, G. and Heymans, H. S. A. Deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome.Biochem. Biophys. Res. Commun. 120 (1984) 179–184PubMedGoogle Scholar
- Schutgens, R. B. H., Schrakamp, G., Wanders, R. J. A., Heymans, H. S. A., Moser, H. W., Moser, A. E., Tager, J. M., van den Bosch, H. and Aubourgh, P. The cerebrohepato-renal (Zellweger) syndrome: prenatal detection based on impaired biosynthesis of plasmalogens.Prenat. Diagn. 5 (1985) 337–344PubMedGoogle Scholar
- Singh, I., Moser, A. E., Goldfischer, S. and Moser, H. W. Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy.Proc. Natl. Aci. USA 81 (1984) 4203–4207Google Scholar
- Trijbels, J., Monnens, L., Bakkeren, J. and van Raay-Selten, A. Biochemical studies in the cerebro-hepato-renal syndrome of Zellweger: a disturbance in the metabolism of pipecolic acid.J. Inher. Metab. Dis. 2 (1979) 39–42Google Scholar
- Wanders, R. J. A., van Weringh, G., Schrakamp, G., Tager, J. M., van den Bosch, H. and Schutgens, R. B. H. Deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase in thrombocytes of Zellweger patients: a simple postnatal diagnostic test.Clin. Chim. Acta 151 (1985a) 217–221PubMedGoogle Scholar
- Wanders, R. J. A., Schutgens, R. B. H. and Tager, J. M. Peroxisomal matrix enzymes in Zellweger syndrome: activity and subcellular localisation in liver.J. Inher. Metab. Dis. 8 Suppl. 2 (1985b) 151–152Google Scholar
- Wanders, R. J. A., van Roermund, C. M. T., de Vries, C. T., van den Bosch, H., Schrakamp, G., Tager, J. M., Schram, A. W. and Schutgens, R. B. H. Peroxisomal β-oxidation of palmitoyl-CoA in human liver homogenates and its deficiency in the cerebro-hepatorenal (Zellweger) syndrome.Clin. Chim. Acta 159 (1986a) 1–10PubMedGoogle Scholar
- Wanders, R. J. A., Purvis, Y. R., Heymans, H. S. A., Bakkeren, J. A. J. M., Parmentier, G. G.et al. Age-related differences in plasmalogen content of erythrocytes from patients with the cerebro-hepato-renal (Zellweger) syndrome: implications for postnatal detection of the disease.J. Inher. Metab. Dis. 9 (1986b) 335–342PubMedGoogle Scholar
- Wanders, R. J. A., Heymans, H. S. A., Schutgens, R. B. H., van Eldere, J. and Eyssen, H. J. Impaired cholesterol side chain cleavage activity in liver from patients with the cerebro-hepato-renal (Zellweger) syndrome in relation to the accumulation of di- and trihydroxy-coprostanoic in serum from the patients.J. Inher. Metab. Dis. 9, Suppl. 2 (1986c) 321–324PubMedGoogle Scholar
- Wanders, R. J. A., Schrakamp, G., van den Bosch, H., Tager, J. M. and Schutgens, R. B. H. A prenatal test for the cerebro-hepato-renal (Zellweger) syndrome by demonstration of the absence of catalase-containing particles (peroxisomes) in cultured amniotic fluid cells.Eur. J. Pediatr. 145 (1986d) 136–138PubMedGoogle Scholar