Stereological analysis of peroxisomes and mitochondria in intestinal epithelium of patients with peroxisomal deficiency disorders: Zellweger's syndrome and neonatal‐onset adrenoleukodystrophy

Abstract

Peroxisomes, participants in lipid metabolism, have been shown to be altered in liver in two metabolic diseases in which long-chain fatty acids accumulate in tissues: Zellweger's syndrome and neonatal adrenoleukodystrophy (ALD). The intestine also plays a role in lipid metabolism, and we have had the opportunity to compare peroxisomes in normal intestinal epithelium with those from patients with Zellweger's syndrome and neonatal ALD at the electron microscopic level by using the combined techniques of cytochemistry and stereological analysis. Peroxisomes were numerous in intestinal epithelium of the normal individuals. They were ellipsoidal in shape with average diameters of 0.37 by 0.56 micron and filled with coarsely granular, DAB+ content. Peroxisomes in the intestinal epithelium of the ALD patient were similar in appearance and number but smaller in size (0.28 by 0.44 micron). Peroxisomes of normal appearance were absent from the intestinal epithelium of patients with Zellweger's syndrome; DAB+ content, however, was observed in rare, membrane-bound structures of much smaller size (0.12 by 0.19 micron). In liver of patients with Zellweger's syndrome, peroxisomes are lacking; in neonatal ALD they are abnormal in appearance and greatly reduced in number. The presence of rare minute peroxisomes in the intestinal epithelium in Zellweger's syndrome and of small peroxisomes in this epithelium in neonatal ALD indicate that peroxisomes in the intestinal epithelium are affected in these diseases, but to a lesser extent than in the liver. In the ALD intestinal epithelium, DAB+ material was also seen in long, sinuous, tubular or cisternal elements intermingled and occasionally in continuity with peroxisomes. It is suggested that these represent the early stages of peroxisome formation, the peroxisomal reticulum as originally envisioned by Lazarow, while the rare structures seen in Zellweger's represent rudiments of such a reticulum. Lamellar inclusions and clear spaces occurred in the cytoplasm adjacent to these structures indicating either that material accumulated there had been extracted during fixation or that these regions are more susceptible to autolysis. Mitochondria are also involved in lipid metabolism and have been reported to be abnormal in Zellweger's tissue. No qualitative differences were observed in the mitochondria of the intestinal epithelia examined in this study. Although quantitation revealed a greater mean volume, number, and surface density of mitochondria in the intestinal epithelia of neonatal ALD, it was not a statistically significant difference in all cases.

Biogenesis of peroxisomes: immunocytochemical investigation of peroxisomal membrane proteins in proliferating rat liver peroxisomes and in catalase-negative membrane loops.

“…These authors suggested that the ghosts represented PO membranes which could not import the matrical proteins because of defects in the translocation machinery. Moreover, long sinuous tubules with positive DAB content were described in the intestinal epithelial cells of a patient with neonatal adrenoleukodystrophy (11). The possible relationship of the ghost-like structures in fibroblasts and the sinuous tubules in intestinal epithelial cells with the double-membraned loops noted in the present study deserves further investigation.…”

Peroxisomes and Peroxisomal Enzymes in the Human Fetal Small Intestine

“…Lazarow et al [27] mentioned the existence of round and elongated peroxisomes in the small intestine of a normal child. In the stereological analysis of peroxisomes in intes tinal epithelium of patients with Zellweger's syndrome and neonatal-onset adrenoleukodystrophy by Black and Cornacchia [11], the presence of tubular forms is obvious in chil dren. Roels et al [28] performed a detailed morphometric study of the two peroxisomal populations in human adult intestine.…”

“…Despite the fact that peroxisomal altera tions have been reported in the intestinal epi thelium of neonates with Zellweger's syn drome and adrcnoleukodystrophy [11], to our knowledge no studies have been devoted to peroxisomes during the development of the human fetal intestine in contrast to the devel opment of the liver [12][13][14][15][16][17] and kidney [18], Therefore, the purpose of the present in vestigation was to analyze the ontogenesis, distribution and enzyme expression of intesti nal peroxisomes from 11-to 22-week human fetuses.…”

Peroxisome assembly mutations in humans: Structural heterogeneity in Zellweger syndrome

“…Morphologically recognizable peroxisomes were first reported missing in the liver and kidney of patients with the genetic disease, Zellweger syndrome, by Goldfischer et al (1973). A deficiency of peroxisomes in a variety of cell types from Zellweger patients has been widely confirmed, although a few residual peroxisomes have occasionally been noted (Arias et al, 1985;Black and Cornacchia, 1986;Lazarow and Moser, 1989). Consistent with the apparent absence of the organelle, many peroxisomal enzymes are missing (Tager et al, 19851, even though they are synthesized normally (Schram et al 1986).…”