X-Linked Adrenoleukodystrophy via the ABCD1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1081 ABCD1$780.00 81405 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Over 93% of patients with X-ALD are caused by ABCD1 mutations which can be detected by Sanger sequencing. Gross deletions/duplications account for the remaining ~7% of causative mutations (; Steinberg et al. 2012).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ABCD1$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features

X-linked adrenoleukodystrophy (X-ALD) is a congenital neurodegenerative disorder due to deficient beta-oxidation of very long-chain fatty acids (VLCFAs) in peroxisomes. It is the most common inherited peroxisomal disorder and affects 1 in 18,000 individuals (Steinberg et al. 2012; Kemp et al. 2012). 

In affected male hemizygotes, the two main clinical phenotypes are cerebral X-ALD (CALD) and adrenomyeloneuropathy (AMN). CALD is the most severe form of X-ALD associated with rapid progression of inflammatory cerebral demyelization. The first symptoms of CALD usually appear between the age of 4 and 12 years as behavioral problems, such as attention deficit and hyperactivity. Then the patients rapidly develop severe neurologic and cognitive deterioration, including blindness, deafness, cerebella ataxia, seizures, dementia, hemiplegia or quadriparesis, and often die within two to five years after diagnosis. AMN is the milder, adult form of X-ALD with the age of onset between 20 and 30 years. Unlike CALD, AMN is a slowly progressive distal axonopathy disorder which affects sensory ascending and motor descending spinal cord tracts. The clinical presentation includes stiffness or weakness of legs, impaired sphincter control, sexual dysfunction, alopecia, and spastic paraplegia. Up to 20% of AMN male patients may develop CALD symptoms later. Adrenocortical insufficiency (Addison disease) is found in most boys with CALD and in about 70% of males with AMN. About 10% of affected males present with adrenocortical insufficiency only, but may develop AMN phenotype later in life (Steinberg et al. 2012; Kemp et al. 2012; Berger et al. 2014).  
Approximately 20- 65% of heterozygous female carriers develop milder AMN symptoms with an average onset later than in males (age > 40 years). Cerebral X-ALD has been reported in a few female cases, but is extremely rare. Adrenal function usually is normal in female carriers, and less than 5% of female AMN patients have adrenocortical insufficiency (Steinberg et al. 2012; Kemp et al. 2012).


X-linked adrenoleukodystrophy is inherited in an X-linked recessive manner, and the ABCD1 gene is the only known genetic cause of X-ALD. ABCD1 contains 10 exons and encodes a transmembrane protein that transports VLCFAs (C24:0, C26:0 and others) into the peroxisomes for beta-oxidation. The penetrance is 100% in male hemizygotes. Approximately 20- 65% of heterozygous female carriers develop the disorder due to skewed X-inactivation. Gonadal or gonosomal mosaicism has been observed. About 4-12% of reported patients have a de novo ABCD1 mutation (Wang et al. 2011; Shimozawa et al; 2011; Kemp et al. 2001). Of over 1,500 reported mutations, ~60% are missense substitutions, ~22% frame shifts, ~10% nonsense mutations, ~3% amino acid deletions/insertions and 3-6% gross deletions/duplications (; Steinberg et al. 2012; Kemp et al. 2001; Shimozawa et al. 2011). Reported missense mutations are commonly found in the transmembrane domain or in the ATP binding domain, and rarely in the C-terminal 52 amino acids (693-745) (Kemp et al. 2012). There is no phenotype-genotype correlation established. The same mutations can result in all different X-ALD phenotypes (Kemp et al. 2001).

Testing Strategy

Our DNA sequencing involves bidirectional Sanger DNA sequencing of all coding exons of ABCD1 plus ~10 bp of flanking non-coding DNA on either side of each exon. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Individuals with clinical symptoms of X-ALD. 


Official Gene Symbol OMIM ID
ABCD1 300371
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Adrenoleukodystrophy 300100


Genetic Counselors
  • Berger J, Forss-Petter S, Eichler FS. 2014. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 98: 135–142. PubMed ID: 24316281
  • Kemp S, Berger J, Aubourg P. 2012. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim. Biophys. Acta 1822: 1465–1474. PubMed ID: 22483867
  • Kemp S, Pujol A, Waterham HR, Geel BM van, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW. 2001. ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum. Mutat. 18: 499–515. PubMed ID: 11748843
  • Shimozawa N, Honda A, Kajiwara N, Kozawa S, Nagase T, Takemoto Y, Suzuki Y. 2011. X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan. J. Hum. Genet. 56: 106–109. PubMed ID: 21068741
  • Steinberg SJ, Moser AB, Raymond GV. 2012. X-Linked Adrenoleukodystrophy. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301491
  • Wang Y, Busin R, Reeves C, Bezman L, Raymond G, Toomer CJ, Watkins PA, Snowden A, Moser A, Naidu S, Bibat G, Hewson S, et al. 2011. X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Mol. Genet. Metab. 104: 160–166. PubMed ID: 21700483
  • X-linked Adrenoleukodystrophy Database
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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