Adrenoleukodystrophy: A Clinical, Pathological and Biochemical Study

Abstract

The association of diffuse cerebral demyelination and adrenal disease was first adequately described by Siemerling and Creutzfeldt in 1923 (13). The report of Siemerling and Creutzfeldt was followed by similar isolated case studies. Despite the startling nature of these reports, the association of adrenal atrophy and cerebral demyelination was considered coincidental, and these cases were usually described as melanodermic leukodystrophy or brown Schilder’s disease. The studies of Gagnon and Leblanc in 1959 (4), Hoefnagel et al. in 1962 (5) and especially Fanconi et al. in 1963 (3) established this combination of neurologic and endocrine abnormalities as a hereditary disease, probably with a sex-linked recessive transmission. Since that time there have been at least 40 well-documented cases. Blaw, in 1971, introduced the term adrenoleukodystrophy (ALD) to describe this condition (1). Our identification, in 1972 of specific light microscopic cytoplasmic changes in the adrenal cortical cells of nine males diagnosed as having Schilder’s disease (10), and the subsequent ultrastructural characterization of the inclusions (7), led to the recognition of similar abnormal inclusions in Schwann cells, testis, and brain (8, 11, 12).