General description

Adrenoleukodystrophy (ALD) is an X-linked recessive disorder caused by mutations in the ABCD1 gene, which is located on chromosome Xq28. This genetic defect impairs peroxisomal beta-oxidation of very long-chain fatty acids (VLCFAs), leading to their accumulation in plasma and tissues, particularly in the nervous system and adrenal cortex. As a result, the disease causes demyelination in the cerebral white matter and dysfunction of the adrenal glands.

ALD manifests in several forms, including childhood cerebral, adolescent cerebral, adult cerebral, adrenomyeloneuropathy (AMN), olivo-ponto-cerebellar, Addisonian, and female-onset, each with distinct clinical courses and prognoses. The severity of neurological and endocrine involvement varies depending on the phenotype, but the genotype does not predict the disease progression, making individual outcomes difficult to determine.

ALD can be triggered by trauma or stress in individuals with an ABCD1 mutation. A similar trauma-induced progression of symptoms is observed in other demyelinating diseases, such as Alexander disease and Vanishing white matter disease (VWMD).

Childhood cerebral form

Childhood cerebral adrenoleukodystrophy most commonly occurs between the ages of 5 and 10, often presenting with symptoms such as abnormal behavior, impaired vision and hearing, poor academic performance, and spastic gait, frequently accompanied by adrenal insufficiency resembling Addison's disease. Following onset, the disease progresses relatively rapidly, often resulting in decerebrate rigidity within a few years.

Adolescent cerebral form

The adolescent cerebral form (onset between ages 11 and 21) presents with symptoms similar to those of the childhood cerebral form but progresses somewhat more slowly.

Adult cerebral form

The adult cerebral form (onset after age 22) presents with dementia, psychiatric symptoms, spastic paraplegia, dysuria, and erectile dysfunction, and progresses relatively rapidly.

Adrenomyeloneuropathy (AMN)

Adrenomyeloneuropathy (AMN) typically develops after puberty, with spastic gait as the primary symptom. It may also be accompanied by dyspraxia, dysuria, and mild sensory disturbances.