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X-linked adrenoleukodystrophy; Siemerling-Creutzfeldt disease; Bronze-Schilders disease; melanodermic leukodystrophy
Epidemiology: rare
Pathology:
1) peroxisomal metabolic disorder
2) adrenocortical insufficiency
3) progressive multifocal demyelination of the CNS
4) neurodegeneration & mental deterioration
5) corticospinal tract dysfunction
6) cortical blindness
Genetics:
1) X-linked, occurs in boys
2) associated with defects in ABCD1 gene
Clinical manifestations: (see pathology)
- different phenotypes including childhood & adult forms & Addison's disease only form
Laboratory:
- evidence of adrenal cortical dysfunction
a) hypglycemia may be observed
b) hyponatremia may be observed
c) low to normalserum cortisol
a) abnormal cosyntropin stimulation test
- adrenoleukodystrophy protein in fibroblasts
* also see ARUP consult [5]
Complications:
- fatal disease
Management:
- gene therapy from autologous hematopoietic stem cells in connection with a retroviral vector used for inserting the ABCD1 gene into ~10% of cell, bone marrow ablation & reintroduction of the transfected cells arrested demyelination & to preserved neurological & cognitive function for longer than a year in 2 boys [3]
- infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector [4]
Related
ATP-binding cassette sub-family D member 1; adrenoleukodystrophy protein; ALDP (ABCD1, ALD)
chromosomal aberration
General
adrenoleukodystrophy
X-linked disease
Properties
DEFICIENCY: LIGNOCEROYL-COA-LIGASE
Database Correlations
OMIM 300100
References
- UniProt :accession P33897
- OMIM :accession 300100
- Cartier N et al
Hematopoietic stem cell gene therapy with a lentiviral
vector in X-linked adrenoleukodystrophy.
Science 2009 Nov 6; 326:818
http://dx.doi.org/10.1126/science.1171242
PMID: 19892975
- Naldini L.
A comeback for gene therapy.
Science 2009 Nov 6; 326:805
PMID: 19892968
http://dx.doi.org/10.1126/science.1181937
- Eichler F, Duncan C, Musolino PL et al
Hematopoietic stem cell gene therapy for cerebral
adrenoleukodystrophy.
N Engl J Med. 2017; 377:1630-1638. Online Oct 4, 2017
PMID: 28976817
- Engelen M
Optimizing treatment for cerebral adrenoleukodystrophy in
the era of gene therapy
N Engl J Med. Oct 4 2017
PMID: 28976819
- ARUP Consult: X-Linked Adrenoleukodystrophy
The Physician's Guide to Laboratory Test Selection & Interpretation
https://arupconsult.com/content/x-linked-adrenoleukodystrophy
- ARUP Consult: X-Linked Adrenoleukodystrophy Testing
https://arupconsult.com/ati/x-linked-adrenoleukodystrophy-testing