Adreno-leukodystrophy (sex-linked Schilder's disease). A pathogenetic hypothesis based on ultrastructural lesions in adrenal cortex, peripheral nerve and testis

Abstract

Striated adrenal cells in the zona reticularis and inner fasciculata apparently constitute the initial adrenolytic lesion in patients with adreno-leukodystrophy (ALD). Cytoplasmic ballooning and macrovacuolization develop after the striations, and probably represent exaggerated responses to adrenocorticotropin (ACTH). Intracytoplasmic lamellae and lamellar-lipid profiles, containing a free 3beta-hydroxysterol, are the ultrastructural correlates of the striations seen with the light microscope. The ultrastructural demonstration of intracytoplasmic lamellae and lamellar-lipid profiles in adrenal striated cells, testicular interstitial cells, Schwann cells and brain macrophages from patients with ALD provides further morphologic evidence for a systemic metabolic defect common to the nervous and endocrine systems. In our experience, adrenal biopsy has proven to be the most effective procedure for the diagnosis of adreno-leukodystrophy. An hypothesis proposing a membrane abnormality affecting its stability and turnover might explain the concomitant destruction of adrenal cortex and brain in these patients.