🧬 Genetic Disorder

Adrenoleukodystrophy

Also known as: ALD, X-linked Adrenoleukodystrophy, X-ALD, Schilder's disease (variant)

Adrenoleukodystrophy (ALD) is a genetic disorder characterized by the buildup of very long-chain fatty acids (VLCFAs) in the brain, nervous system, and adrenal glands. This accumulation disrupts normal cellular function, leading to a range of neurological and hormonal problems. The most common form, X-linked ALD, primarily affects males due to its X-linked inheritance pattern. Different phenotypes exist, varying in severity and age of onset, from childhood cerebral ALD (CCALD) to adrenomyeloneuropathy (AMN) in adulthood.

ICD-10: E71.3 Orphanet: 68 OMIM: 300100
👥 1 in 17,000 males Prevalence
🔬 30 Active Trials

ALD is like having a problem with your body's garbage disposal system. It can't break down certain fats, so they build up and cause damage, especially in the brain and adrenal glands. This can lead to problems with thinking, moving, and making hormones.

Signs & Symptoms

  • Behavioral problems
  • Vision problems
  • Hearing loss
  • Muscle weakness
  • Seizures
  • Adrenal insufficiency
  • Cognitive decline
  • Spasticity
  • Skin hyperpigmentation
  • Gait abnormalities

Treatment Options

GENE THERAPY

Hematopoietic Stem Cell Transplantation (HSCT)

HIGHLY EFFECTIVE
GENE THERAPY FDA Approved

Gene Therapy (elivaldogene autotemcel)

HIGHLY EFFECTIVE Approved 2021
MEDICATION

Lorenzo's Oil

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Adrenal hormone replacement therapy

HIGHLY EFFECTIVE
THERAPY

Physical therapy

SUPPORTIVE
SUPPORTIVE

Symptomatic management

SUPPORTIVE

Diagnosis

  • Plasma VLCFA measurement
  • Genetic testing (ABCD1 gene)
  • MRI of the brain
  • Adrenal function tests
  • Neurological examination

History

Adrenoleukodystrophy was first described by Siemerling and Creutzfeldt in 1923. The genetic basis of X-linked ALD was discovered in 1993 with the identification of the ABCD1 gene. Lorenzo's oil, a mixture of glyceryl trioleate and glyceryl trierucate, was developed in an attempt to reduce VLCFA levels and was popularized by the film 'Lorenzo's Oil'.

Recent Breakthroughs

2021

FDA Approves Gene Therapy for Adrenoleukodystrophy

The FDA approved elivaldogene autotemcel (Skysona), a gene therapy for boys with early, active cerebral adrenoleukodystrophy (CALD). This therapy involves using the patient's own stem cells, modified to carry a functional copy of the ABCD1 gene.