Restoration of biochemical function of the peroxisome in the temperature-sensitive mild forms of peroxisome biogenesis disorder in humans

We have found that peroxisome assembly is temperarure-sensitive (ts) in mil d forms of peroxisome biogenesis disorders (PBDs), that is all infantile Re fsum disease (IRD) patients and a few neonatal adrenoleukodystrophy patient s of several complementation groups. The number of peroxisomes increased da ily in incubation at 30 degrees C in the ts cells. Oxidation of very long-c hain fatty acids, processing of acyl-CoA oxidase and dihydroxyacetonephosph ate acyltransferase activity also improved after 8 days incubation at 30 de grees C in thr IRD fibroblasts. These biochemical functions of the peroxiso me did not change at 30 degrees C in Zellweger fibroblasts. Number of perox isomes gradually decreased after 4 days when the temperature shifted from 3 0 to 37 degrees C in the ts cells. These results indicate that the biochemi cal functions of peroxisome are also restored by incubation at 30 degrees C in the mild and ts phenotype of PBDs, and the results will aid to predict the severity and the prognosis of affected children. (C) 2000 Elsevier Scie nce B.V. All rights reserved.