- Ronald JA Wanders, PhD
Ronald JA Wanders, PhD
- Professor of Clinical Enzymology of Inborn Errors of Metabolism
- University of Amsterdam
- Florian S Eichler, MD
Florian S Eichler, MD
- Associate Professor of Neurology
- Harvard Medical School
- Section Editors
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Sihoun Hahn, MD, PhD
Sihoun Hahn, MD, PhD
- Section Editor — Genetics
- Professor of Pediatrics
- University of Washington School of Medicine, Seattle Children's Hospital
Adrenoleukodystrophy (ALD; MIM #300100) is a peroxisomal disorder of beta-oxidation that results in accumulation of very long chain fatty acids in all tissues. ALD consists of a spectrum of phenotypes (including adrenomyeloneuropathy [AMN]) that vary in the age and severity of clinical presentation (table 1A-C) [1,2]. These conditions are known as the ALD/AMN complex.
The pathophysiology, clinical manifestations, and treatment of ALD will be reviewed here. Other peroxisomal disorders, including neonatal ALD, are discussed separately. (See "Peroxisomal disorders".)
ALD is the most common peroxisomal disorder . In a report that included data from the two laboratories that perform most of the assays for the disorder, the minimum frequency in the United States was estimated at 1 in 21,000 and 1 in 16,800 for hemizygotes and hemizygotes plus heterozygotes, respectively .
ALD is an X-linked disorder. It is caused by mutations in the adenosine triphosphate (ATP)-binding cassette (ABC), subfamily D, member 1 gene (ABCD1 gene), located at Xq28, that encodes an ABC transporter, similar to cystic fibrosis transmembrane conductance regulator (CFTR) [5-9]. The ABC transporter helps form the channel through which very long chain fatty acids move into the peroxisome, probably as coenzyme A (CoA)-esters . The phenotype does not correlate with the type of mutation.
ABCD1 mutations may prevent normal transport of very long chain fatty acids (VLCFAs) into peroxisomes, thereby preventing beta-oxidation and breakdown of VLCFAs. Accumulation of abnormal VLCFAs in affected organs (central nervous system [CNS], Leydig cells of the testes, and the adrenal cortex) is presumed to underlie the pathologic process of the adrenoleukodystrophies (ALD) . However, plasma VLCFA levels do not predict phenotype and cell-specific functions of ABCD1 may play a role in the pathogenesis independent of VLCFA .
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- CLINICAL FEATURES
- Childhood cerebral forms
- Addison disease only
- Other presentations
- Female carriers
- Newborn screening
- Laboratory testing
- Visual evoked responses
- Adrenal insufficiency
- Hematopoietic cell transplantation
- Dietary therapy
- Pharmacologic therapy
- Gene therapy
- SUMMARY AND RECOMMENDATIONS