The natural history of X-linked adrenoleukodystrophy (ALD) was determined by questionnaire survey in a nation-wide retrospective study of 145 patients at Gifu University School of Medicine, and the Ministry of Health, Labor and Welfare, Japan. The various forms of ALD included childhood cerebral in 46 patients, adrenomyeloneuropathy [AMN] (39), adult cerebral (33), adolescent (14), and olivo-ponto-cerebellar [OPC] (13). Initial symptoms were different in the various forms: in the childhood cerebral form, these were intellectual and visual disturbances; gait and sensory disturbances characterized the AMN form; psychic and gait disorders in the adult cerebral form; visual and gait symptoms in the adolescent form; and gait disturbance in the OPC form. Age of onset influenced rate of progression: rapid in the under age 8 years, and more slowly in the over 8 year group. Half the patients with AMN and OPC had developed cerebral symptoms at 10 years after onset. [1]

COMMENT. X-linked adrenoleukodystrophy is a neurodegenerative disease with demyelination, adrenal insufficiency and accumulation of very-long chain saturated fatty acids. The childhood cerebral form of ALD accounts for 32% of cases in Japan, and the AMN form (27%) is the second most common phenotype. ALD occurs in 1:30,000 and 1:50,000 boys in Japan, compared to 1:20,000 to 1;200,000 in other countries (Bezman and Moser, 1998). Based on the above study, ALD should be classified according to age of onset as well as the clinical phenotype, in evaluating success of treatment. A rapid rate of progression is expected in younger patients, and those with ataxia would be expected to develop cerebral symptoms later.