X-Linked Adrenoleukodystrophy, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease characterized by magnetic resonance imaging findings in the white matter, adrenocortical insufficiency, and abnormal plasma concentrations of very long chain fatty acids. The phenotypic expression of X-ALD varies widely. The phenotypes can be subdivided into 3 main categories: childhood cerebral form, adrenomyeloneuropathy (AMN), and Addison disease only. The childhood cerebral form has an onset of symptoms between ages 4 and 8, beginning with attention deficit hyperactivity disorder-like symptoms with progressive cognitive, behavior, vision, hearing, and motor deterioration. AMN usually presents in males in their late twenties as progressive paraparesis, sexual dysfunction, sphincter disturbances, and abnormalities in adrenocortical function. The Addison only phenotype typically presents by age 7.5 with adrenocortical insufficiency without significant neurological involvement. Most of these patients eventually develop AMN. Some female carriers may experience mild AMN symptoms with a later age of onset.
The phenotype cannot be predicted by very long chain fatty acids (VLCFA) plasma concentration or by the nature of the mutation. The same mutation can be associated with each of the known phenotypes. Different phenotypes often co-occur within a family.
Testing for plasma concentration of VLCFA (ACRN / Acylcarnitines, Quantitative, Plasma) is the preferred first-tier screening method for X-ALD. This is abnormal in 99% of affected males and 85% of carrier females. Sequencing of the ABCD1 gene is available to confirm the diagnosis of X-ALD, improve carrier detection, and assist with prenatal diagnosis.
Confirming a diagnosis of X-linked adrenoleukodystrophy when a familial mutation has previously been identified
Carrier screening of at-risk individuals when a mutation in the ABCD1 gene has been identified in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order XALDS / X-Linked Adrenoleukodystrophy, Full Gene Analysis.
Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations in this gene or in other genes that may be associated with X-linked adrenoleukodystrophy.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Moser HW, Mahmood A, Raymond GV: X-linked adrenoleukodystrophy. Nat Clin Pract Neurol 2007 Mar;3(3):140-151
2. Wang Y, Busin R, Reeves C, et al: X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Mol Genet Metab 2011 Sep-Oct;104(1-2):160-166
3. Kemp S, Berger J, Aubourg P: X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 2012 Sept;1822(9):1465-1474