X-linked adrenoleukodystrophy

Elevated circulating long chain fatty acid concentration

In X-linked adrenoleukodystrophy, a faulty ABCD1 gene impairs the way cells break down certain fats, so saturated very long chain fatty acids (VLCFA) build up in the blood, the nervous system, and the adrenal glands. This buildup is the core biochemical signature of the condition.

Abnormal cerebral white matter morphology

In the cerebral form of X-ALD, the brain's white matter (the insulated wiring that connects brain regions) breaks down. MRI shows spreading areas of demyelination, which track with the loss of thinking, vision, and movement skills.

Impaired vibration sensation at ankles

In the adult spinal-cord form of X-ALD (adrenomyeloneuropathy), the nerves carrying position and vibration signals degenerate. People lose the ability to feel vibration in the feet and become unsteady, especially in the dark, a pattern called sensory ataxia.

Seizure

In the childhood cerebral form, seizures can occur as the brain white matter is progressively affected.

Polyneuropathy

Adrenomyeloneuropathy, the adult form of X-ALD, slowly damages both the spinal cord and the peripheral nerves. This combination produces stiff, weak legs together with nerve-related sensory loss that worsens over years.

Urinary bladder sphincter dysfunction

Spinal-cord involvement in X-ALD often disrupts bladder control. People may develop urgency, frequency, or difficulty emptying the bladder as the disease progresses, alongside the leg stiffness of adrenomyeloneuropathy.

Hearing impairment

In the cerebral form of X-linked adrenoleukodystrophy, hearing can be affected. In one pediatric cohort, visual or hearing impairment was among the neurologic symptoms, reported in about a third of children with cerebral disease.

X-linked recessive inheritance

The condition is X-linked: the ABCD1 gene sits on the X chromosome, so males are typically affected, while female carriers may have milder, later-onset symptoms.

Primary adrenal insufficiency

Adrenal insufficiency — adrenal glands that cannot make enough of their hormones — is common in X-linked adrenoleukodystrophy. Across studies most males with X-ALD develop adrenal failure, while it is uncommon in women who carry the condition.

Hyperpigmentation of the skin

When X-ALD damages the adrenal glands, the body makes extra ACTH, which darkens the skin and the linings of the mouth. This bronzing or darkening can be an early outward sign of the adrenal failure that often comes with X-ALD.

Visual impairment

Vision can be affected in the cerebral form of X-linked adrenoleukodystrophy. In one pediatric cohort, visual or hearing impairment was reported in about a third of children with cerebral disease.

Cognitive impairment

The childhood cerebral form brings progressive cognitive decline, along with vision and hearing loss, as demyelination spreads through the brain.

Progressive spastic paraparesis

Adult X-linked adrenoleukodystrophy often shows up as adrenomyeloneuropathy, a slowly worsening problem of the spinal cord and nerves. A central feature is progressive spastic paraparesis: stiffness and weakness in the legs that gets worse over time.

Increased circulating ACTH level

In X-linked adrenoleukodystrophy with adrenal involvement, the pituitary signal ACTH is often raised because the adrenal glands respond poorly. In a small group of adrenomyeloneuropathy patients, all had elevated ACTH at the start.

X-linked adrenoleukodystrophy

Diagnosed using: ABCD1 gene testing.

X-linked adrenoleukodystrophy

Diagnosed using: brain MRI with Loes score.

X-linked adrenoleukodystrophy

Diagnosed using: newborn screening (C26:0-lysophosphatidylcholine).

X-linked adrenoleukodystrophy

Diagnosed using: plasma very long chain fatty acids (VLCFA).

hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation can halt the cerebral form when carried out early (presymptomatic or early-symptomatic), which is why newborn screening matters; it does not reverse damage that has already occurred.

Used to help with: X-linked adrenoleukodystrophy.

adrenal hormone replacement

Adrenal hormone (steroid) replacement is needed by everyone who develops adrenal insufficiency; it treats the adrenal failure but does not stop the neurological disease.

Used to help with: X-linked adrenoleukodystrophy.

allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation is used for the early cerebral form of X-linked adrenoleukodystrophy. It has been reported to work when given before symptoms appear or very early, and in a pediatric cohort early-stage cerebral patients who received a transplant trended toward better survival.

Used to help with: X-linked adrenoleukodystrophy.

elivaldogene autotemcel (Skysona)

Elivaldogene autotemcel, sold as Skysona, is a gene therapy for the cerebral form of X-linked adrenoleukodystrophy. It was first approved in the EU in 2021 for early cerebral disease in patients under 18 with an ABCD1 mutation when a matched sibling stem-cell donor is not available.

Used to help with: X-linked adrenoleukodystrophy.

Lorenzo's oil

Lorenzo's oil is a dietary fat mixture studied in X-linked adrenoleukodystrophy. It did not prove effective for the inflammatory cerebral form, though the review noted that people without symptoms, possibly some adrenomyeloneuropathy cases without brain involvement, and female carriers might benefit from it together with a diet low in very long chain fats. Its benefit remains limited and uncertain.

Used to help with: X-linked adrenoleukodystrophy.