Rare Diseases: Zellweger syndrome

Zellweger syndrome is a rare hereditary disorder affecting infants, and usually results in death. Unusual problems in prenatal development, an enlarged liver, high levels of iron and copper in the blood, and vision disturbances are among the major manifestations of Zellweger syndrome.

The PXR1 gene has been mapped to chromosome 12; mutations in this gene cause Zellweger syndrome. The PXR1 gene product is a receptor found on the surface of peroxisomes - microbodies found in animal cells, especially liver, kidney and brain cells. The function of peroxisomes is not fully understood, although the enzymes they contain carry out a number of metabolically important reactions. The PXR1 receptor is vital for the import of these enzymes into the peroxisomes: without it functioning properly, the peroxisomes can not use the enzymes to carry out their important functions, such as cellular lipid metabolism and metabolic oxidations.

There is a yeast homolog to human PXR1, which should allow powerful molecular genetic techniques to be used in the investigation of the normal role of peroxisomes in cells, as well as the molecular events that occur in disease states.