Zellweger syndrome is one of a group of four related diseases called peroxisome biogenesis disorders (PBD), which are part of a larger group of diseases known as the leukodystrophies. These are inherited conditions that damage the white matter of the brain and also affect how the body metabolizes particular substances in the blood and organ tissues. Zellweger syndrome is the most severe of the PBDs. Infantile Refsum disease (IRD) is the mildest, and neonatal adrenoleukodystrophy and rhizomelic chondrodysplasia have similar but less severe symptoms. The PBDs are caused by defects in genes that are active in brain development and the formation of myelin, the whitish substance found in the cerebral cortex area of the brain. After birth, defects in the same genes reduce or eliminate the presence of peroxisomes – cell structures that break down toxic substances in the cells of the liver, kidneys, and brain. As a result, in Zellweger syndrome, high levels of iron and copper build up in blood and tissue and cause the characteristic symptoms of the disease. These symptoms include an enlarged liver; facial deformities such as a high forehead, underdeveloped eyebrow ridges, and deformed ear lobes; and neurological abnormalities, such as mental retardation and seizures. Infants with Zellweger syndrome also lack muscle tone, sometimes to the point of being unable to move, and may not be able to suck or swallow. Some babies will be born with glaucoma, retinal degeneration, and impaired hearing. Jaundice and gastrointestinal bleeding may also occur.
There is no cure for Zellweger syndrome, nor is there a standard course of treatment. Since the metabolic and neurological abnormalities that cause the symptoms of Zellweger syndrome are caused during fetal development, treatments to correct these abnormalities after birth are limited. Most treatments are symptomatic and supportive.
The prognosis for infants with Zellweger syndrome is poor. Most infants do not survive past the first 6 months, and usually succumb to respiratory distress, gastrointestinal bleeding, or liver failure.
Prepared by the National Institutes of Health