Temperature sensitivity in peroxisome assembly processes characterizes milder forms of peroxisome biogenesis disorders.

[neonatal adrenoleukodystrophy]

Peroxisome biogenesis disorders (PBDs ) contain various clinical phenotypes ; Zellweger syndrome (ZS ), neonatal adrenoleukodystrophy (NALD ), and infantile Refsum disease (IRD ), decreasing in the clinical severity in this order . We found that all IRD cell lines and some NALD lines belonging to several different complementation groups are temperature-sensitive in peroxisome assembly ; that is , they lacked catalase -positive peroxisomes at 37 degrees C , but do gain the peroxisomes at 30 degrees C . We identified heterozygous mutations E 55 K /R 119 Stop in the PEX 2 gene of an IRD patient of complementation group F . The E 55 K mutation was the direct cause of the temperature-sensitivity because similar phenotypes could be transferred to PEX 2 -defective CHO cells by transfecting the mutant gene . Thus , temperature-sensitive peroxisome assembly is representative of milder forms of PBDs .