X-linked adrenoleukodystrophy; Siemerling-Creutzfeldt disease; Bronze-Schilders disease; melanodermic leukodystrophy
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Epidemiology
rare
Pathology
- peroxisomal metabolic disorder
- adrenocortical insufficiency
- progressive multifocal demyelination of the CNS
- neurodegeneration & mental deterioration
- corticospinal tract dysfunction
- cortical blindness
Genetics
Clinical manifestations
(see pathology)
- different phenotypes including childhood & adult forms & Addison's disease only form
Laboratory
- evidence of adrenal cortical dysfunction
- hypglycemia may be observed
- hyponatremia may be observed
- low to normalserum cortisol
- abnormal cosyntropin stimulation test
- adrenoleukodystrophy protein in fibroblasts
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]
More general terms
Additional terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P33897.html
- ↑ OMIM https://mirror.omim.org/entry/300100
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/19892975
Naldini L. A comeback for gene therapy. Science 2009 Nov 6; 326:805 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19892968 <Internet> http://dx.doi.org/10.1126/science.1181937 - ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/28976817
Engelen M Optimizing treatment for cerebral adrenoleukodystrophy in the era of gene therapy N Engl J Med. Oct 4 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28976819 - ↑ 5.0 5.1 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