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GENATLAS PHENOTYPE
last update : 19-10-2013
Symbol ALD
Location Xq28
Name X-linked adrenoleukodystrophy
Other name(s)
  • adrenomyeloneuropathy
  • Siemerling-Creutzfeldt disease
  • Bronze Schilder disease
  • melanodermic leukodystrophy
    • Corresponding gene ABCD1
    Other symbol(s) X-ALD, AMN
    Main clinical features
  • progressive cerebral demyelination cerebral childhood adrenoleukodystrophy (CCALD) or spinal cord neurodegeneration (adrenomyeloneuropathy, AMN), adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFA) in tissues
  • wide range of phenotypic expression including:
  • the rapidly progressive often letal childhood neurodegenerative disorder;
  • adrenomyeloneuropathy, which presents as slowly progressive paraparesis in adults, mental retardation
  • and Addison disease without neurologic manifestations
    • approximately 50% of female carriers develop a spastic paraparesis secondary to myelopathic changes similar to adrenomyeloneuropathy
    Genetic determination sex linked
    Prevalence approximately 1:20,000 males
    Function/system disorder metabolism/peroxisomal
    Type disease
    Gene product
    Name peroxisomal membrane protein that is a member of the ATP-binding cassette transporter superfamily; ATP-binding cassette transporters perform energy-dependent transmembrane solute trafficking
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   absent protein about 61 percent
    frameshift   absent protein about 23 percent
    nonsense   absent protein about 10 percent
    insertion-deletion   absent protein about 4 percent
    deletion   absent protein large deletion in at least 3 percent
    deletion   absent protein AG deletion at nucleotide 1801-1802 is the most common recurring mutation observed in 8 percent of families
    Remark(s)
  • result in accumulation of very long chain fatty acids
  • mutant His-ALDP (Y174C), which has a mutation between transmembrane domain 2 and 3, did not exhibit peroxisomal localization by immunofluorescense (Takahashi 2007)
  • impaired very long-chain acyl-CoA beta-oxidation in X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction (PMID: 23671276))
  • significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms (PMID: 23768953))
    • Genotype/Phenotype correlations phenotypic expression and prognosis of an affected male is unpredictably variable