Zellweger syndrome amniocytes: Morphological appearance and a simple sedimentation method for prenatal diagnosis

Zellweger syndrome is the prototype of a growing group of genetic diseases caused by an absence or deficiency of peroxisomes. The defect causes the enzyme catalase to remain in the cytosol instead of being packaged into peroxisomes. This mislocalization can be easily detected by sedimentation analysis. Amniocytes were homogenized and then centrifuged to pellet organelles. Catalase was found to sediment with the peroxisomes in the homogenates of normal cells, but to remain in the supernatant with Zellweger syndrome amniocyte homogenates. This striking difference is unambiguous and reproducible, and provides a simple method for prenatal diagnosis. Moreover, it allows one to differentiate diseases in which peroxisomes are deficient from other peroxisomal diseases in which the organelle is intact, but one enzyme is defective. Electron microscopic observations support the biochemical determinations. Normal amniocytes contain small peroxisomes in which a weak cytochemical reaction for catalase may be demonstrated. Zellweger amniocytes appear to lack these organelles, although some cells have rare structures that might be residual or abnormal peroxisomes.