Characterization of X-linked adrenoleukodystrophy in different biological specimens from ten Portuguese families
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X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disease characterized by progressive demyelination, adrenocortical insufficiency and accumulation in tissues and body fluids of unbranched, saturated very long-chain fatty acids (VLCFA). The diagnosis of ALD is usually based on clinical history, neurological examination and the determination of levels of VLCFA in plasma and cultured skin fibroblasts.
In the present paper we report the biochemical findings in plasma, cultured skin fibroblasts and lymphoblastoid cell lines from ALD patients. The results obtained indicate that the increment of the ratios C24:0 to C22:0 and C26:0 to C22:0 and of the concentration C26:0 (µg/ml) in plasma was parallel with that of fibroblasts, but not with that of Epstein-Barr virus (EBV)-transformed lymphocytes, suggesting that this cell line is not reliable for diagnosis of ALD by VLCFA analysis.
Subsequent studies carried out on family members revealed heterozygotes other than obligate carriers and hemizygotes who were pre-symptomatic or had a misdiagnosis of multiple sclerosis or psychosis.
KeywordsFamily Member Multiple Sclerosis Neurodegenerative Disease Body Fluid Neurological Examination
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- Antoku Y, Ohtsuka Y, Nagara H et al (1989) A comparison of erythrocytes, lymphocytes and plasma as samples in fatty acid analysis for the diagnosis of adrenoleukodystrophy.J Neurol Sci 94: 193–200.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
- 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 21: 240–249.Google Scholar
- Jorge PM, Quelhas MD, Soares P, Nogueira AM, Miranda MC (1992) Adrenoleucodistrofia: Estudo em doentes que Apresentam Apenas Insuficiência da Glândula Suprarrenal.Arquivos de Medicina 6: 129–132.Google Scholar
- Harnden DG (1960) A human skin culture technique used for cytological examinations.Br J Exp Pathol 41: 31–35.Google Scholar
- Harkness RA, Lynes GW, Johnson AW (1992) The efficacy of very-long-chain fatty acid analysis in the diagnosis of peroxisomal disorders: an audit report.J Inher Metab Dis 15: 287–288.Google Scholar
- Moser HW (1989) X-linked adrenoleukodystrophy. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic Basis of Inherited Disease, 6th edn. New York: McGraw-Hill, 1511–1532.Google Scholar
- Moser HW, Moser AB, Kawamura N et al (1980) Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts.Ann Neurol 7: 542–549.Google Scholar
- Moser HW, Moser AB, Frayer KK et al (1981) Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids.Neurology 31: 1241–1246.Google Scholar
- Moser HW, Moser AB, Trojak JE, Supplee SW (1983) Identification of female carriers of adrenoleukodystrophy.J Pediatr 103: 54–59.Google Scholar
- Moser HW, Moser AB, Singh I, O'Neill BP (1984) Adrenoleukodystrophy: survey of 303 cases: biochemistry, diagnosis, and therapy.Ann Neurol 16: 628–641.Google Scholar
- Moser HW, Moser AB, Naidu S, Bergin A (1991) Clinical aspects of adrenoleukodystrophy and adrenomyeloneuropathy.Dev Neurosci 13: 254–261.Google Scholar
- Moser HW, Moser AB, Smith KD et al (1992) Adrenoleukodystrophy: phenotypic variability and implications for therapy.J Inher Metab Dis 15: 645–664.Google Scholar
- Neitzel H (1986) A routine method for the establishment of permanent growing lymphoblastoid cell lines.Hum Genet 73: 320–326.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
- Wanders RJA, Roermund CWT, Schutgens RBH et al (1990) The inborn errors of peroxisomal β-oxidation: a review.J Inher Metab Dis 13: 4–36.Google Scholar
- Watkins PA, Naidu S, Moser HW (1987) Adrenoleukodystrophy: biochemical procedures in diagnosis, prevention and treatment.J Inher Metab Dis 10: 46–53.Google Scholar