Tuesday, May 26, 2015 | 05:33 AM

Madisons Foundation - Moms And Dads In Search Of Needed Support

Zellweger Syndrome
Monday, 13 October 2003
Wednesday, 18 February 2004
cerebrohepatorenal syndrome


Zellweger syndrome is a genetic disorder caused by the loss and abnormal function of peroxisomes, which are a part of every cell. This disorder is characterized by abnormal brain and nervous system development, low muscle tone, typical facial appearance, and a large liver. The greatest impact of this disease is on brain development and the function of the entire nervous system. Children affected with Zellweger syndrome are usually diagnosed at or soon after birth.


Zellweger syndrome is estimated to occur in 1 per 50,000 births and is found equally in males and females. This syndrome is inherited as an autosomal recessive disorder. This means that the abnormal genes that cause this disease are passed on to a child by both parents. Genes occur in pairs, one half of the pair comes from the mother and the other half from the father. Because this is an autosomal recessive disorder, both parents must have an abnormal gene which they pass on when an embryo is conceived. It is important to remember that parents do not have any control over which genes are transmitted when a baby is conceived.

Signs and Symptoms

The clinical picture is dominated by extremely low tone and severe seizures. The effect on the brain is profound. Characteristic facial features include a prominent forehead, widely spaced eyes, abnormally shaped and positioned ears, high arched roof of the mouth, and a chin that is smaller than normal. There is flattening of the back of the skull, a large “soft spot” and excessive skin folds on the neck. Additionally, there is severely low muscle tone and weakness, usually beginning at birth. This muscle weakness can cause an inability to suck and swallow and affect the ability to breath. Infants are also prone to seizures, hearing loss, vision problems and mental retardation. The liver can become enlarged. The heart can also have various abnormalities. Because of the hypotonia and flattened facies, these infants are sometimes suspected to have Down syndrome.

Possible Causes

This disorder is caused by the poor function of structures within cells called peroxisomes. Peroxisomes are needed for normal fat processing. Abnormal changes in a gene located on chromosome 12, named PXR1, have been found to cause Zellweger syndrome. Changes in this PXR1 gene can lead to defective enzymes within peroxisomes which are needed for the normal functioning of peroxisomee. Zellweger syndrome is generally associated with problems in virtually all peroxisomal functions. Abnormal peroxisomes disrupt the development of nerve fibers and this leads to brain and nervous system malformation. Cells could also be damaged by the accumulation of toxins which result from the malfunction of various enzymes found in peroxisomes. This could contribute to the various problems found in Zellweger syndrome.


Genetic testing can be done to determine whether there is an abnormal change in the PXR1 gene. There are also now at least 10 other known genes to be involved with this disease. The diagnosis can also be made by evaluating for deficiency of the enzymes. Further blood tests can also support the diagnosis.


There is no cure for Zellweger syndrome, and treatment is based on the symptoms that are present. Experiments with diet supplementation are on going but effectiveness is difficult to evaluate.


Zellweger syndrome causes severe brain damage and eventual liver failure. Most of these infants show little evidence of development. They feed poorly and fail to thrive unless tube fed. Seizures usually begin within the first days of life and are very difficult to control. Children with Zellweger syndrome rarely survive beyond 1 year of age. Death usually occurs 6 months after the onset of the disease, and is usually due to breathing problems, bleeding in the digestive system, or liver failure. The spectrum of Zellweger syndrome can greatly vary and some children are only mildly affected. Because of this large degree of variation it is very difficult to give a specific life expectancy or prognosis.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


Zellweger Syndrome
This is the personal website of a French child named Jason. It has his story, information about the syndrome, as well as the possibility to chat.

National Institute of Neurological Diseases and Stroke
A well written article on the syndrome with links to ongoing research.

Google Search for Zellweger Syndrome

References and Sources

Behrman: Nelson Textbook Pediatrics, 16th ed., Zellweger syndrome, www.home.mdconsult.com Genes and Disease www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.240 PEDBASE www.icondata.com/health/pedbase/files/ZELLWEGE.HTM National Institute of Neurological Diseases and Stroke www.ninds.nih.gov/health_and_medical/disorders/zellwege_doc.htm