A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts.

[zellweger syndrome]

Zellweger spectrum disorders (ZSD ) are diagnosed by biochemical assay in blood , urine and cultured fibroblasts and PEX gene mutation identification . In most cases studies in fibroblasts corroborate results obtained in body fluids . In 1996 Clayton and colleagues described a 10 -year old girl with evidence of a peroxisome disorder , based on elevated bile acid metabolites and phytanate . At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect . Studies in our laboratory showed that she also had elevated plasma pipecolate , supporting the former diagnosis . Despite the abnormal metabolites detected in blood (phytanate , bile acid intermediates and pipecolate ), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results . In addition , she had a milder clinical phenotype than usually associated with ZSD . Since complementation analysis to determine the gene defect was not possible , we screened this patient following the PEX Gene Screen algorithm (PGS ). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis . Two mutations in PEX 10 were identified , a frameshift mutation inherited from her father and a de novo missense mutation in a conserved functional domain on the other allele . This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum . Furthermore , it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver .