VLCFA Screening — X-ALD & Peroxisomal Disorders

What is X-linked adrenoleukodystrophy (X-ALD)?

X-linked adrenoleukodystrophy is an inherited metabolic disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal transporter protein essential for the import of very long-chain fatty acids (VLCFAs) into peroxisomes for beta-oxidation. Without functional ABCD1, VLCFAs accumulate in plasma, red blood cells, and tissues, leading to progressive demyelination of the central nervous system, adrenal cortex dysfunction, and peripheral nerve involvement.

X-ALD affects approximately 1 in 17,000 births. The childhood cerebral form (CCALD) manifests between ages 4 and 10 with rapid, devastating neurological decline. Adrenomyeloneuropathy (AMN) typically appears in the second to third decade with slower progression. Without early detection, the cerebral form causes irreversible loss of motor and cognitive function.

What does the test measure?

The LPC-VLCFA screening test quantifies lysophosphatidylcholine (LPC) derivatives of very long-chain fatty acids from a dried blood spot using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with stable isotope-labelled internal standards:

• C26:0-LPC — the primary diagnostic marker; significantly elevated in X-ALD and peroxisomal disorders
• C24:0-LPC — elevated in affected individuals, supporting diagnostic confirmation
• C22:0-LPC — used as the denominator in the key diagnostic ratio
• C26:0/C22:0 ratio — exhibits excellent separation between healthy individuals and affected patients, providing the highest diagnostic sensitivity and specificity

LPC-VLCFA measurement in dried blood spots is superior to traditional plasma VLCFA quantification: LPC derivatives are more stable in the DBS matrix at ambient temperature, require minimal sample volume, and have demonstrated higher diagnostic sensitivity and specificity in newborn screening programmes worldwide.

Who is this test for?

The LPC-VLCFA screening test is designed for B2B partners integrating rare disease screening into their clinical pathways, newborn screening programmes, or diagnostic workflows:

• Newborn screening programmes: National and regional screening laboratories seeking to add X-ALD to their expanded newborn screening panel. LPC-VLCFA testing from heel-prick DBS is the recommended first-tier screening method.
• Paediatric neurologists: Clinicians investigating children with unexplained neurological regression, white matter abnormalities on MRI, or suspected leukodystrophy where X-ALD must be ruled out.
• Metabolic disease clinics: Specialist centres diagnosing and monitoring patients with suspected peroxisomal disorders, including Zellweger spectrum disorders, ACOX1 deficiency, and D-bifunctional protein (DBP) deficiency.
• Carrier screening: Genetic counselling services and reproductive health providers screening female carriers of ABCD1 mutations to enable family counselling and reproductive planning.

Clinical significance

Early detection saves lives

Hematopoietic stem cell transplantation (HSCT) is currently the only accepted therapy capable of halting disease progression in the cerebral form of X-ALD — but only when performed before symptom onset or very early in the disease course, before irreversible neurological damage occurs. This makes presymptomatic detection through newborn screening critically important.

Peroxisomal disorder spectrum

Beyond X-ALD, elevated LPC-VLCFA levels indicate impaired peroxisomal beta-oxidation and can identify a spectrum of related disorders:

• Zellweger spectrum disorders — caused by PEX gene defects leading to generalised peroxisomal dysfunction
• ACOX1 deficiency — isolated peroxisomal acyl-CoA oxidase-1 deficiency
• DBP deficiency — D-bifunctional protein deficiency affecting VLCFA oxidation

Carrier detection

Female carriers of ABCD1 mutations may remain asymptomatic or develop a milder neurological syndrome later in life. LPC-VLCFA screening can identify carriers, enabling genetic counselling, family cascade screening, and informed reproductive decisions.

Sample collection

A simple finger-prick or heel prick is used to collect a few drops of blood onto a dried blood spot (DBS) card. The LPC-VLCFA analytes are highly stable in the DBS matrix at room temperature, making this collection method ideal for:

• Newborn screening — standard heel-prick collection
• Remote and resource-limited settings — no cold chain required
• Worldwide shipping — DBS cards can be transported by standard mail
• Extended storage — analyte stability at ambient temperature for prolonged periods

Results are delivered via our secure portal within 3–5 working days of sample receipt and include quantitative LPC-VLCFA values, diagnostic ratios, and interpretive commentary. For branded or white-label reporting, contact us to discuss customisation options for your organisation.