Skip to main content
SpringerLink
Log in

X-linked adrenoleukodystrophy: Biochemical diagnosis and enzyme defect

  • The X Chromosome
  • Published:
Journal of Inherited Metabolic Disease

Summary

The adrenoleukodystrophies refer to three genetically distinct disorders all characterized by the accumulation of very long-chain fatty acids. In this paper we will review the biochemical aspects of these leukodystrophies with particular emphasis on the methods used to measure very long-chain fatty acid levels in plasma and their reliability. Furthermore, we will concentrate on the primary defect in the X-linked form of adrenoleukodystrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aubourg P, Bougneres PF, Rocchiccioli G (1985) Capillary gas-liquid chromatographic-mass spectrometric measurement of very long chain (C22 to C26) fatty acids in microliter samples of plasma.J. Lipid Res 26: 263–267.

    Google Scholar 

  • Bakkeren, JAJM, Monnens LAH, Trijbels JMF, Maas JM (1984) Serum very long chain fatty acid pattern in Zellweger syndrome.Clin Chim Acta 138: 325–331.

    Google Scholar 

  • Blaw ME (1970) Melanodermic type leukodystrophy. In Vinken PJ, Bruyn GW, eds.Handbook of Clinical Neurology, vol. 10. Amsterdam: North-Holland, 128–133

    Google Scholar 

  • Caruso U, Fowler B, Erceq M, Romaro C (1991). Determination of very-long-chain fatty acids in plasma by a simplified gas chromatographic-mass spectrometric procedure.J Chromatogr (Biomed Appl) 562: 147–152.

    Google Scholar 

  • Fanconi A, Prader A, Isler W, Luthy F, Siebenman F (1963) Morbus Addison mit Hirnsklerose im Kindesalter: ein hereditäres Syndrom mit X-chromosomaler Vererbung.Helv Paediatr Acta 18: 480–510.

    Google Scholar 

  • Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues.J Biol Chem 226: 497–509.

    Google Scholar 

  • Hashmi M, Stanley W, Singh I (1986) Lignoceroyl-CoASH ligase: enzyme defect in fatty acidβ-oxidation systems in X-linked childhood adrenoleukodystrophy.FEBS Lett 196: 347–350.

    Google Scholar 

  • Igarashi M, Schaumburg HH, Powers JN, Kolodny E, Suzuki K (1976) Fatty acid abnormality in adrenoleukodystrophy.J Neurochem 26: 851–860.

    Google Scholar 

  • Jakobs BS, Wanders RJA (1991) Conclusive evidence that very long chain fatty acids are oxidized exclusively in peroxisomes in human skin fibroblasts.Biochem Biophys Res Commun 178: 842–847.

    Google Scholar 

  • Johnson AB, Schaumburg HH, Powers JN (1976) Histochemical characteristics of the striated inclusions of adrenoleukodystrophy.J Histochem Cytochem 24: 725–730.

    Google Scholar 

  • Kawamura N, Moser HW, Kishimoto Y (1981) Very long chain fatty acid oxidation in rat liver.Biochem Biophys Res Commun 99: 1216–1225.

    Google Scholar 

  • Lageweg W, Sykes JEC, Lopes-Cardozo M, Wanders RJA (1991a) Oxidation of very-long-chain fatty acids in brain: cerotic acid isβ-oxidized exclusively in rat brain peroxisomes.Biochim Biophys Acta 1085: 381–384.

    Google Scholar 

  • Lageweg W, Tager JM, Wanders RJA (1991b) Topography of very-long-chain acyl-CoA synthetase in peroxisomes from rat liver.Biochem J 276: 53–56.

    Google Scholar 

  • Lageweg W, Wanders RJA, Tager JM (1991c) Long-chain acyl-CoA synthetase and very-long-chain acyl-CoA synthetase activities in peroxisomes and microsomes from rat liver: an enzymological study.Eur J Biochem 196: 519–523.

    Google Scholar 

  • Lazarow PB, Moser HW (1989) Disorders of peroxisome biogenesis. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic Basis of Inherited Disorders. New York: McGraw-Hill, 1479–1509.

    Google Scholar 

  • Lazo O, Contreras M, Hashmi M, Stanley W, Irazu C, Singh I (1988) Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy.Proc Natl Acad Sci USA 85: 7647–7651.

    Google Scholar 

  • Lazo O, Contreras M, Singh I (1990). Topographical localization of peroxisomal acyl-CoA ligases: differential localization of palmitoyl-CoA and lignoceroyl-CoA ligases.Biochemistry 29: 2981–2986.

    Google Scholar 

  • Lepage G, Roy CC (1986) Direct transesterification of all classes of lipids in a one-step reaction.J Lipid Res 27: 114–120.

    Google Scholar 

  • Moser HW, Moser A (1989) X-linked adrenoleukodystrophy. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 1511–1532.

    Google Scholar 

  • Moser HW, Moser AB (1991) Measurement of saturated very long chain fatty acids in plasma. In Hommes FA, ed.Techniques in Diagnostic Human Biochemical Genetics. New York: Wiley-Liss, 177–203.

    Google Scholar 

  • Moser HW, Moser AB, Kawamura N et al (1980) Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts.Ann Neurol 7: 524–549.

    Google Scholar 

  • Moser HW, Moser AB, Frayer KK et al (1981) Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids.Neurology 31: 1241–1249.

    Google Scholar 

  • Nagamatsu K, Soeda S, Mori M, Kishimoto Y (1985) Lignoceroyl-coenzyme A synthetase from developing rat brain: partial purification, characterization and comparison with palmitoyl-CoA synthetase activity and liver enzymes.Biochim Biophys Acta 836: 80–83.

    Google Scholar 

  • Nagamatsu K, Soeda S, Kishimoto Y (1986) Change of substrate specificity of rat liver microsomal fatty acyl-CoA synthetase activity by Triton X-100.Lipids 21: 328–332.

    Google Scholar 

  • Numa S (1981) Two long-chain acyl coenzyme A synthetases: their different roles in fatty acid metabolism and its regulation.Trends Biochem Sci 6: 113–15.

    Google Scholar 

  • Onkenhout W, Van der Poel PFH, van den Heuvel MPM (1989) Improved determination of very-long-chain fatty acids in plasma and cultured skin fibroblasts: application to the diagnosis of peroxisomal disorders.J Chromatogr (Biomed Appl) 494: 31–41.

    Google Scholar 

  • Poll-Thé B-T, Roels F, Ogier H et al (1988) A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase.Am J Hum Genet 42: 422–434.

    Google Scholar 

  • Powers JM, Schaumburg HH (1974) Adrenoleukodystrophy: similar ultrastructural changes in adrenal cortical and Schwann cells.Arch Neurol 30: 406–408.

    Google Scholar 

  • Reubsaet FAG, Veerkamp JH, Bakkens SGF, Trijbels JMF, Monnens LAH (1989) Total and peroxisomal oxidation of various saturated and unsaturated fatty acids in rat liver, heart and M. quadriceps.Lipids 24: 945–950.

    Google Scholar 

  • Reubsaet FAG, Veerkamp JH, Brückwilder MLP, Trijbels JMF, Hashimoto T, Monnens LAH (1991) Immunochemical and biochemical studies of fatty acid oxidation in fibroblasts of Zellweger and X-linked adrenoleukodystrophy patients.Biochim Biophys Acta 1083: 305–309.

    Google Scholar 

  • Schaumburg JN, Powers JN, Suzuki K, Raine CS (1974) Adrenoleukodystrophy (sex-linked Schilder's Disease): ultrastructural demonstration of specific cytoplasmic inclusions in the central nervous system.Arch Neurol 31: 210–213.

    Google Scholar 

  • Siemerling E, Creutzfeld HG (1925) Bronzekrankheit und sklerosierende Enzephalomyelitis.Arch Psychiatr 68: 217–244.

    Google Scholar 

  • Stellaard F, ten Brink HJ, Kok RM, van den Heuvel L, Jakobs C (1990) Stable isotope dilution analysis of very long chain fatty acids in plasma, urine and amniotic fluid by electron capture negative ion mass fragmentography.Clin Chim Acta 192: 133–144.

    Google Scholar 

  • Singh H, Poulos A (1988) Distinct long chain and very long chain fatty acyl-CoA synthetases in rat liver microsomes and peroxisomes.Arch Biochem Biophys 266: 486–495.

    Google Scholar 

  • Singh H, Derwas N, Poulos A (1987) Very long chain fatty acidβ-oxidation by rat liver mitochondria and peroxisomes.Arch Biochem Biophys 359: 382–390.

    Google Scholar 

  • Singh H, Usher S, Poulos A (1989) Mitochondrial and peroxisomal oxidation of stearic and lignoceric acids by rat brain.J Neurochem 53: 1711–1718.

    Google Scholar 

  • Singh I, Moser HW, Moser AB, Kishimoto Y (1981). Adrenoleukodystrophy: impaired oxidation of long chain fatty acids in cultured skin fibroblasts and adrenal cortex.Biochem Biophys Res Commun 102: 1223–1229.

    Google Scholar 

  • Singh I, Moser AB, Goldfischer S, Moser HW (1984) Lignoceric acid is oxidized in the peroxisome; implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy.Proc Natl Acad Sci USA 81: 4203–4207.

    Google Scholar 

  • Singh I, Bhusnan A, Relan NR, Hashimoto T (1988) Acyl-CoA ligases from rat brain microsomes: an immunochemical study.Biochim Biophys Acta 963: 509–514.

    Google Scholar 

  • Soeda S, Kishimoto Y, Hashimoto I (1986). Immobilization of fatty acyl-CoA synthetase: effect on its stability and substrate specificity.Biochem Int 12: 225–233.

    Google Scholar 

  • Tanaka T, Hosaka T, Hoshimaru M, Numa S (1979) Purification and properties of long-chain acyl coenzyme A synthetase from rat liver.Eur J Biochem 98: 165–172.

    Google Scholar 

  • Tanaka Y, Ando S, Tsuji S, Miyatake T (1988) Enhanced synthesis of hexacosanoic acid in cultured skin fibroblasts from patients with ALD.Biomed Res 9: 451–456.

    Google Scholar 

  • Tsuji S, Sano T, Ariga T, Miyatake T (1981) Increased synthesis of hexacosanoic acid (C26:0) by cultured skin fibroblasts from patients with ALD and AMN.J Biochem 90: 1233–1236.

    Google Scholar 

  • Tsuji S, Ohno T, Miyatake T, Suzuki A, Yamakawa T (1984) Fatty acid elongation activity in fibroblasts from patients with adrenoleukodystrophy.J Biochem 96: 1241–1247.

    Google Scholar 

  • Ulrich J, Hershkowitz N, Heitz P, Sigrist T, Baerlocher P (1978) Adrenoleukodystrophy: preliminary report of a connatal case.Acta Neuropathol 43: 77–83.

    Google Scholar 

  • Veerkamp JH, van Moerkerk HTB (1986) Peroxisomal fatty acid oxidation in rat and human tissues: effect of nutritional state, clofibrate treatment and postnatal development in the rat.Biochim Biophys Acta 875: 301–310.

    Google Scholar 

  • Wanders RJA, van Roermund CWT, van Wijland MJA et al (1987a) X-linked adrenoleukodystrophy: defective peroxisomal oxidation of very long chain fatty acids but not of very long chain fatty acyl-CoA esters.Clin Chim Acta 165: 321–329.

    Google Scholar 

  • Wanders RJA, van Roermund CWT, van Wijland MJA et al (1987b) Peroxisomal fatty acidβ-oxidation in relation to the accumulation of very long chain fatty acids in peroxisomal disorders.J Clin Invest 80: 1778–1788.

    Google Scholar 

  • Wanders RJA, Heymans HSA, Schutgens RBH, Barth PG, van den Bosch H, Tager JM (1988a) Peroxisomal disorders in neurology.J Neurol Sci 88: 1–39.

    Google Scholar 

  • Wanders RJA, van Roermund CWT, van Wijland MJA et al (1988b) Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids.Biochem Biophys Res Commun 153: 618–624.

    Google Scholar 

  • Wanders RJA, Schelen A, Feller N et al (1990a) First prenatal diagnosis of acyl-CoA oxidase deficiency.J Inher Metab Dis 13: 371–374.

    Google Scholar 

  • Wanders RJA, van Roermund CWT, Schelen A, Schutgens RBH, van den Bosch H, Tager JM (1990b) X-linked adrenoleukodystrophy and other inborn errors of peroxisomalβ-oxidation: clinical and biochemical aspects. In Uziel G, Wanders RJA, Cappa M, eds.Adrenoleukodystrophy and Other Peroxisomal Disorders. Amsterdam: Elsevier, 17–36.

    Google Scholar 

  • Wanders RJA, van Roermund CWT, Schutgens RBH et al (1990c) The inborn errors of peroxisomalβ-oxidation: a review.J Inher Metab Dis 13: 4–36.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University Hospital of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    R. J. A. Wanders, W. Lageweg & R. B. H. Schutgens

  2. Deparmtent of Clinical Biochemistry, University Hospital of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    R. J. A. Wanders, C. W. T. van Roermund, W. Lageweg, B. S. Jakobs, R. B. H. Schutgens & A. A. Nijenhuis

  3. Department of Biochemistry, University Hospital of Amsterdam, Meibergdreef 9, 1105 AZ, Ansterdam, The Netherlands

    J. M. Tager

Authors
  1. R. J. A. Wanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. W. T. van Roermund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Lageweg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. S. Jakobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. B. H. Schutgens
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. A. Nijenhuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. M. Tager
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wanders, R.J.A., van Roermund, C.W.T., Lageweg, W. et al. X-linked adrenoleukodystrophy: Biochemical diagnosis and enzyme defect. J Inherit Metab Dis 15, 634–644 (1992). https://doi.org/10.1007/BF01799620

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01799620

Keywords

Search

Navigation