Zellweger syndrome

A rare group of autosomal recessive inherited disorders characterized by the reduction or absence of peroxisomes in the tissues. Signs and symptoms include increased levels of iron and copper in the blood and tissues, hepatomegaly, facial abnormalities, mental retardation, seizures, and hypotonia.

Zellweger spectrum disorders

It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies.

History

Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.

Other Names

Cerebrohepatorenal syndrome; CHR; ZWS; ZS; Zellweger leukodystrophy See Less

Symptoms

• The signs and symptoms of Zellweger syndrome typically become apparent within the first few hours or days of life.
• Affected newborns often have poor muscle tone (hypotonia); seizures; feeding difficulties; liver cysts with liver dysfunction; vision loss; hearing loss; and distinctive facial characteristics including a flattened face, broad nasal bridge, high forehead, upslanting palpebral fissures, and epicanthal folds.
• Some people also have an abnormally small or large head size (microcephaly or macrocephaly, respectively); protruding tongue; neck skin folds; cataracts; glaucoma; and/or nystagmus.
• Many affected infants have skeletal abnormalities, which may include a large space between the bones of the skull and bone spots known as chondrodysplasia punctata that can be seen with an X-ray.
• The function of the central nervous system (brain and spinal cord) is typically severely affected. Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys.

Cause

• Zellweger syndrome is an autosomal recessive condition caused by changes (mutations) in any one of at least 12 different genes that are involved in the creation and proper function of peroxisomes.
• Mutations in the genes responsible for Zellweger syndrome cause dysfunction of peroxisomes, which leads to the signs and symptoms of the condition.
• Almost 70% of individuals with a Zellweger spectrum disorder have a mutation in the PEX1 gene.
• The other genes associated with the Zellweger spectrum each account for a smaller percentage of cases.

Inheritance

• Zellweger syndrome is inherited in an autosomal recessive manner.
• This means that a person must have a change (mutation) in both copies of the responsible gene in order to have the condition.
• The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers.
• Carriers do not have signs or symptoms of the condition.
• When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Diagnosis

A diagnosis of a Zellweger syndrome is usually suspected when characteristic signs and symptoms are present at birth, including the distinctive facial features.

Tests

• Tests that measure or detect specific substances in blood or urine samples can confirm a diagnosis of Zellweger syndrome.
• For example, detection of elevated levels of very long chain fatty acids (VLCFA) in the blood is the most commonly used screening test.
• Additional tests on blood and urine samples to find other substances associated with the condition may be performed.
• An ultrasound may be used to look for cysts on the kidneys or an enlarged liver.
• A genetic test to find a mutation in one of the genes associated with Zellweger spectrum disorders may also be used to confirm the diagnosis.

Genetic testing

• Clinical genetic testing is available for the twelve genes known to cause Zellweger syndrome.
• Carrier testing for at-risk relatives and prenatal testing are possible if the two disease-causing mutations in the family are known.
• The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests.
• The intended audience for the GTR is health care providers and researchers.
• Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Testing Resources

• The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition.
• The intended audience for the GTR is health care providers and researchers.
• Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

• There is currently no cure or effective treatment for Zellweger syndrome.
• Management is supportive and based on the signs and symptoms present in each person.
• For example, infants with feeding issues may require placement of a feeding tube to ensure proper intake of calories.
• Care is usually handled by a team of specialists that may include pediatricians, neurologists, surgeons, audiologists (treat hearing problems), ophthalmologists (treat vision problems), and orthopedists (treat skeletal abnormalities).

Prognosis

• The prognosis for infants with Zellweger syndrome is very poor.
• Most infants do not survive past the first 6 months of life, and usually succumb to respiratory distress, gastrointestinal bleeding, or liver failure.
• Although no specific treatment for Zellweger syndrome currently exists, significant progress has been made in understanding the molecular and biochemical aspects of the condition, which researchers believe will lead to new research strategies and new therapies in the future.

Zellweger-Syndrome at NINDS

Zellweger syndrome at NIH's Office of Rare Diseases

Zellweger syndrome Resources
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