Indications for Testing
Laboratory testing for X-ALD is used to
- Screen infants (as part of newborn screening panels in some states)
- Infants with positive newborn screening results
- Boys with signs of childhood cerebral adrenoleukodystrophy (CCALD), such as attention deficit disorder/hyperactivity, and increasing cognitive, visual, behavioral, and motor impairment, particularly with adrenocortical dysfunction
- Males with signs of adrenomyleoneuropathy, such as leg stiffness or weakness, sexual dysfunction, sphincter impairment, or adrenocortical dysfunction
- Males with AI and normal 21-hydroxylase antibody testing (VLCFA profile)
- Detect carrier status or disease in family members of a patient diagnosed with X-ALD
- Monitor for disease progression and to guide treatment in patients diagnosed with X-ALD
Newborn screening for X-ALD involves measurement of C26:0-LPC, a derivative of a VLCFA marker, in dried blood spots. Neonates with increased levels of C26:0-LPC are referred for confirmatory tests. Some states perform DNA sequencing to detect ABCD1 gene variants before referring the patient for confirmatory tests. See Genetic Testing below.
VLCFA concentrations are typically increased in male patients with X-ALD, regardless of disease status or patient age. Three specific VLCFAs are useful in diagnostic testing: behenic acid (C22:0), tetracosanoic acid (C24:0), and hexacosanoic acid (C26:0). Measurement of VLCFAs in plasma (specifically C26:0, the ratio of C26:0 to C22:0, and the ratio of C24:0 to C22:0) can be used to diagnose X-ALD in males, and has a high sensitivity for the disease. In 15-20% of females with X-ALD, VLCFA concentrations will be normal, and genetic testing must be performed for a definitive diagnosis.
All patients with X-ALD have an ABCD1 gene variant; genetic testing therefore is typically used to definitively diagnose the disease and to identify female carriers. This testing is particularly indicated in females because only about 85% will demonstrate elevated VLCFA concentrations.
Testing of family members is recommended following a diagnosis of X-ALD. However, the detection of variants is not prognostic because there is no genotype-phenotype correlation (ie, the particular variant does not correlate with disease severity or disease course), even among family members. In addition, up to 19% of patients with X-ALD have been reported to carry de novo ABCD1 variants.
Monitoring is necessary in patients with X-ALD to detect disease progression and identify patients for whom treatment is indicated. It includes testing for AI (measurement of morning cortisol and adrenocorticotropic hormone [ACTH]) and periodic evaluation for cerebral white matter demyelination via magnetic resonance imaging (MRI).
Risk for AI in males with X-ALD is age-dependent. Testing for the development of AI is recommended every 4-6 months for patients ≤10 years of age and annually for patients 11-40 years of age. In patients ≥40 years, the risk of developing AI is lower; testing is recommended if clinically indicated but does not need to occur at the same frequency as in younger populations. AI is rare in women with X-ALD. See the Adrenal Insufficiency topic for additional information on laboratory testing.