X-LINKED ADRENOLEUKODYSTROPHY: CLINICAL CHARACTERISTICS, DIAGNOSIS AND MANAGEMENT

Περίληψη

Adrenoleukodystrophy (X-ALD) is a rare X-linked peroxisomal disease, which usually presents in affected
males with one of three phenotypes: adult-onset adrenomyeloneuropathy (AMN, 45%), childhood-onset
cerebral demyelination (CALD, 35%), or primary adrenal insufficiency (PAI, 10%). Occasionally, X-ALD patients
may suffer from less specific symptoms resembling those of other neurological conditions. Variability
in presentation and age of onset can make the diagnosis challenging. AMN should be considered in patients
presenting with spastic paraparesis. Female carriers manifest a late-onset mild form of myelopathy
and/or neuropathy. Inclusion of testing for X-ALD in newborn screening programs is expected to expand
our understanding of the disorder’s natural history. Newborn screening should enable early detection of
affected individuals and allow timely therapeutic interventions. Such interventions include corticosteroid
replacement therapy for PAI, allogeneic hematopoietic stem cell transplantation for CALD, and approved
gene therapy (elivaldogene autotemcel) for suitable candidates with childhood CALD. Currently, no effective
treatment exists for the neurological manifestations of AMN, the commonest presentation of X-ALD.
Hopefully, in the near future, novel gene therapy approaches, similar to those recently approved for other
rare neurogenetic diseases may also be developed for X-ALD.