Zellweger Syndrome: Causes, Symptoms, Treatment

Zellweger Syndrome

Zellweger syndrome is one of a group of four diseases that are related and are referred to as 'peroxisome biogenesis disorders (PBD). The diseases are a part of a larger group of diseases known as leukodystrophies. They have inherited conditions that damage the white matter in an affected person's brain and how their body metabolizes certain substances in their organ tissues and blood. Zellweger syndrome is the most severe of the PBDs. Of the PBDs, Infantile Refsum disease (IRD) is the mildest form. Neonatal Adrenoleukodystrophy and Rhizomelic Chondrodysplasia present similar yet less severe symptoms. PBDs are caused by defects in a person's genes that are active during the development of a person's brain and the formation of 'myelin,' the whitish substance found in a person's cerebral cortex area.

Main Digest

Once a person with Zellweger syndrome has been born, defects in their genes either reduce or eliminate the presence of 'peroxisomes,' or cell structures that break down toxic substances in the cells of their kidneys, liver, and brain. The result is high levels of copper and iron that build up in their blood and tissue, causing the symptoms that are characteristic of the disease. Zellweger syndrome is also known by the following names:

• Generalized Peroxisomal Disorders
• Peroxisomal Biogenesis Disorders
• Zellweger Syndrome Spectrum
• ZSS

The U.S. Social Security Administration (SSA) has included Zellweger Syndrome as a Compassionate Allowance to expedite a disability claim.

Causes of Zellweger Syndrome

Mutations in one of several genes cause Zellweger syndrome; they lead to a dysfunctional protein that is important for a person's cells to be able to import newly-synthesized proteins into small cytoplasmic organelles called 'peroxisomes.' Zellweger syndrome is characterized by either a reduction in or the complete absence of peroxisomes. Key enzymes are critical for different chemical reactions, particularly oxidation, that are contained within peroxisomes. Structural and functional abnormalities of peroxisomes can lead to disease development observed in Zellweger syndrome.

Peroxisomes are usually abundant in a person's kidney and liver; their lack leaves the organs of persons with Zellweger syndrome affected by the disease. Toxic molecules that enter the person's bloodstream fail to be detoxified because of a lack of peroxisomes, although there are additional mechanisms for detoxification. Peroxisomes may also function in the organic creation of key compounds and play important roles related to different chemical reactions in a person's body. The mutations in several genes and Zellweger syndrome that affect the function of peroxisome include peroxin-1 (PEX1), peroxin-2 (PEX2), peroxin-3 (PEX3), peroxin-5 (PEX5), peroxin-6 (PEX6), and peroxin-12 (PEX12). Each gene location is genetically and biochemically unique and found on different chromosomes.

Symptoms of Zellweger Syndrome

There are several observable clinical features associated with Zellweger syndrome. These symptoms can include facial, developmental, as well as eye defects. Features characteristic of the syndrome include up-slanting eyes, a high forehead, and 'epicanthal,' or skin folds along the person's nasal borders of the space between the upper and lower eyelids of their eyes. Babies with Zellweger syndrome commonly experience a loss of muscle tone, severe weakness, and many times experience seizure activity. Many also have severe ocular (eye) abnormalities that may affect their vision. The symptoms of Zellweger syndrome can include:

• Seizures
• Jaundice
• Elevated iron
• Enlarged liver
• Elevated copper
• Inability to move
• Poor sucking ability
• Vision disturbances
• Lack of muscle tone
• Difficulty swallowing
• Intellectual Disability
• Prenatal growth failure
• Gastrointestinal bleeding
• Characteristic facial characteristics

The more common features of Zellweger syndrome involve enlargement of the person's liver, vision issues, and increased levels of copper and iron in their blood. Some infants with the syndrome experience prenatal growth failure. Symptoms present at birth include a lack of muscle tone and an inability to move. Additional symptoms related to the syndrome may include intellectual disability, characteristic facial features, an inability to either suck or swallow, jaundice, and gastrointestinal bleeding.

The most common features of Zellweger syndrome include an enlarged liver, high levels of iron and copper in the blood, and vision disturbances. Some affected infants may show prenatal growth failure. Symptoms at birth may include a lack of muscle tone and an inability to move. Other symptoms may include unusual facial characteristics, mental retardation, seizures, and an inability to suck and swallow. Jaundice and gastrointestinal bleeding may also occur.

Diagnosing Zellweger Syndrome

The absence of peroxisomes in persons with Zellweger syndrome was initially demonstrated by American pathologist S.L. Goldfischer in 1985. The absence of these organelles in the affected person's liver is now considered the disorder's hallmark. Persons with Zellweger syndrome have been found to present with fewer peroxisomes in their brains and cultured skin fibroblasts. 'Fibroblasts' are a type of skin cell; in Zellweger syndrome, these cells appear to have 'ghost-like' peroxisomes caused by the absence of particular proteins inside the organelles recruited into the membranes.

Peroxisomes play a crucial role in organ development. Brain abnormalities may be explained by the disrupted migration of 'neurons,' or nerve cells, around the third month of gestation. A defect occurs in a particular area of a person's brain called the 'cerebrum,' which leads to small or thick convolutions in the person's brain tissue. The brain abnormality permits Zellweger syndrome to be identified and distinguished from other diseases involving brain abnormalities. Additional tissues involved in the syndrome include the person's kidney, liver, heart, cartilage, and muscle. The majority of persons with Zellweger syndrome have cysts on their kidneys.

A diagnosis of Zellweger syndrome can be reached by measuring the metabolic compounds in the person's blood samples. Various plasmalogens, fatty acids, bile acid intermediates, and pipecolic acid are commonly studied. Other than diminished levels of plasmalogen, the compounds in the person's blood commonly increase in persons affected by Zellweger syndrome. Another possibility is to detect plasmalogen synthesis and fatty acid levels before the person's birth by obtaining cells in the amnion fluid, something referred to as 'amniocentesis.' Pregnant mothers with a baby previously affected by Zellweger syndrome can choose to have a prenatal diagnosis to determine if their child is affected by the syndrome.

Treatment of Zellweger Syndrome

Medical science has not yet discovered a cure for Zellweger syndrome, and there is no standard treatment for this syndrome. Zellweger syndrome and its neurological and metabolic abnormalities are caused during fetal development. Treatments to correct them after a person is born are limited; most treatment options are supportive and symptomatic.

The prognosis for infants with Zellweger syndrome is poor, with most infants failing to survive their first six months of life; they usually die from gastrointestinal bleeding, respiratory distress, or liver failure. People with Zellweger syndrome often do not live more than a year after they are diagnosed. Because of this, genetic counseling and prenatal diagnosis are commonly prioritized for parents who are either identified or concerned that they might be at risk of having a child with Zellweger syndrome.

Author Credentials:

Thomas C. Weiss is a researcher and editor for Disabled World. Thomas attended college and university courses earning a Masters, Bachelors and two Associate degrees, as well as pursing Disability Studies. As a Nursing Assistant Thomas has assisted people from a variety of racial, religious, gender, class, and age groups by providing care for people with all forms of disabilities from Multiple Sclerosis to Parkinson's; para and quadriplegia to Spina Bifida. Explore Thomas' complete biography for comprehensive insights into his background, expertise, and accomplishments.

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Cite This Page (APA): Weiss, T. C. (2010, March 13). Zellweger Syndrome: Causes, Symptoms, Treatment. Disabled World. Retrieved April 18, 2024 from www.disabled-world.com/disability/types/zellweger-syndrome.php

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