Peroxisomal localization of the immunoreactive beta-oxidation enzymes in a neonate with a beta-oxidation defect. Pathological observations in liver, adrenal cortex and kidney.
A boy born to healthy, unrelated parents, presented at birth with hypotonia and seizures. Very long chain fatty acids in the plasma were strongly elevated; bile acid intermediates and plasmalogen biosynthesis were normal. Acyl-CoA oxidase activity was normal. The patient died at the age of 3 months. The cerebellum and medulla oblongata showed neuronal migration defects. The specific biochemical basis for the impaired peroxisomal beta-oxidation has not been found. The three immunoreactive peroxisomal beta-oxidation enzymes and catalase were localized in the hepatocellular peroxisomes. Aberrant features of the peroxisomes included: a subpopulation of organelles larger than 1 micron, an amorphous nucleoid in many organelles, and invaginations of the peroxisomal membrane into the matrix. Peroxisomes in the proximal renal tubules also contained the three immunoreactive beta-oxidation enzymes. Regularly spaced trilamellar inclusions were seen in hepatic macrophages; they were much more abundant in adrenocortical macrophages. The inclusions were birefringent and resistant to acetone extraction. Distinct hepatic fibrosis had developed over a period of 2.5 months. We speculate that the impaired beta-oxidation is due to a defect at the level of the peroxisomal carnitine octanoyl or -acetyl transferase, responsible for the export of beta-oxidation products.
Espeel
M
M
Department of Human Anatomy and Embryology, Free University of Brussels, Belgium.
Roels
F
F
Van Maldergem
L
L
De Craemer
D
D
Dacremont
G
G
Wanders
R J
RJ
Hashimoto
T
T
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000737:chemistry* / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000302:Adrenal Cortex / Q000201:enzymology / Q000473:pathology; D002374:Catalase / Q000737:chemistry; D004746:Enoyl-CoA Hydratase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000473:pathology; D008830:Microbodies / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism
D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002374:Catalase; D042962:Acyl-CoA Oxidase; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase