Adrenoleucodistrofia

Adrenoleukodistrofia (ALD) is a rare X-linked peroxisomal disorder caused by pathogenic variants in the ABCD1 gene. The defect impairs transport of very long-chain fatty acids (VLCFAs) into peroxisomes for degradation, causing VLCFA accumulation in brain white matter and the adrenal glands and leading to progressive demyelination and adrenal dysfunction.

Inheritance: X-linked recessive. Most affected individuals are male; female carriers may develop milder symptoms, such as adrenomyeloneuropathy, later in life.

Clinical forms: The childhood cerebral form develops with behavioral changes, vision problems, and rapid neurological decline. Adrenomyeloneuropathy (AMN) begins in adolescence or adulthood with stiffness, gait disturbance, and sphincter dysfunction. Adrenal insufficiency can occur with or without neurologic symptoms.

Diagnosis: Plasma VLCFA testing shows elevated levels (notably C26:0 and the C24:0/C22:0 ratio). Confirmation is by ABCD1 gene sequencing. MRI commonly shows demyelination in the parieto-occipital white matter. Newborn screening is being piloted in some regions.

Treatment and prognosis: There is no cure for the underlying defect. Adrenal insufficiency is treated with steroid replacement. In early cerebral ALD, allogeneic hematopoietic stem cell transplantation (HSCT) can halt progression. Gene therapy using autologous stem cells with ABCD1 is under investigation with promising early results. Lorenzo’s oil has not proven neurologic benefit. Regular monitoring and supportive care are important. Outcome depends on form and timing of treatment; untreated cerebral ALD progresses to severe disability and death within years.