Adreno-leukodystrophy (sex-linked Schilder's disease). A pathogenetic hypothesis based on ultrastructural lesions in...

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.