Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.

Abstract

X-LINKED adrenoleukodystrophy (ALD; McKusick 300100) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency.^1-5 The classic form of ALD usually has onset in childhood (childhood cerebral ALD; CCALD) between ages 5 and 15 years, with rapid neurologic deterioration, including visual disturbances, spastic tetraplegia, and dementia, leading to a vegetative state within a few years. Adult-onset cerebral ALD (ACALD) also presents with rapidly progressive neurologic dysfunction, leading to a bedridden state usually within 5 years of onset.⁶ Neuropathologically, the cerebral forms of ALD are characterized by demyelination, occasionally associated with inflammatory changes.^7,8 Milder phenotypes such as adrenomyeloneuropathy (AMN)^9,10 and Addison disease only¹¹ also have been recognized. Adrenomyeloneuropathy presents with slowly progressive spastic paraparesis and urinary disturbances because of involvement of the spinal cord and peripheral nerves, with onset in adolescence or adulthood.^9,10 The clinical presentation of ALD can be highly variable, and various phenotypes can be observed even within the same pedigree.^12-14