Fetal globoid cell leukodystrophy

Abstract

The early lesions of globoid cell leukodystrophy in a 110-g, 18-week-old fetus were characterized in relation to fetal myelination, and comparisons made to the animal models of this disease. Uninucleated and binucleated periodic acid-Schiff-positive cells were present in the spinal cord but not in ventral roots within regions at very early stages of myelination. These cells stained with the lectin Ricinus communis agglutinin, which preferentially binds to beta-D-galactosyl residues as found in stored metabolites of globoid cell leukodystrophy. Ultrastructural examination of the spinal cord revealed typical tubular spicular cytoplasmic inclusions in cells corresponding to the periodic acid-Schiff-positive cells. The degree and distribution of myelin tubules and myelination glia was similar to that in weight- and size-matched control fetuses. These results indicate that the first appearance of inclusion-bearing cells is closely associated with the onset of myelination in the central nervous system, apparently earlier in the stage of myelination than occurs in the central nervous system of the mouse model. Characteristic tubular inclusions are also present in renal epithelium in animal models but have not been seen in the human kidney. We have since identified noncharacteristic crystalline inclusions in the kidney of this human fetus.