Rare Gastroenterology News

Disease Profile

Zellweger syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cerebrohepatorenal syndrome; CHR; ZWS;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

Summary

Zellweger syndrome is the most severe form of a spectrum of conditions called Zellweger spectrum. The signs and symptoms of Zellweger syndrome typically appear during the newborn period and may include poor muscle tone (hypotonia), poor feeding, seizureshearing loss, vision loss, distinctive facial features, and skeletal abnormalities.[1][2] Affected children also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys.[2] Children with Zellweger syndrome usually do not survive beyond the first year of life. Zellweger syndrome is caused by mutations in any one of at least 12 genes; mutations in the PEX1 gene are the most common cause. It is inherited in an autosomal recessive manner.[1] There is no cure for Zellweger syndrome; treatment is generally symptomatic and supportive.

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.[1][2][3] 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.[4] 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.[2] The function of the central nervous system (brain and spinal cord) is typically severely affected.[3] Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Corneal opacity
0007957
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
EEG abnormality
0002353
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Epiphyseal stippling
Speckled calcifications in end part of bone
0010655
External ear malformation
0008572
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties in infancy
0008872
Flat face
Flat facial shape
0012368
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
High forehead
0000348
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Profound global developmental delay
0012736
Reduced tendon reflexes
0001315
Respiratory insufficiency
Respiratory impairment
0002093
Severe muscular hypotonia
Severely decreased muscle tone
0006829
Short stature
Decreased body height
Small stature

[ more ]

0004322
Skeletal dysplasia
0002652
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Very long chain fatty acid accumulation
0008167
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal chorioretinal morphology
0000532
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Clitoral hypertrophy
Enlarged clitoris
0008665
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Flat occiput
0005469
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hydronephrosis
0000126
Hypospadias
0000047
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Malabsorption
Intestinal malabsorption
0002024
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Multicystic kidney dysplasia
0000003
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Polymicrogyria
More grooves in brain
0002126
Posterior embryotoxon
0000627
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Pyloric stenosis
0002021
Seizure
0001250
Sensorineural hearing impairment
0000407
Underdeveloped supraorbital ridges
Flattened bony protrusion above eyes
0009891
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
5%-29% of people have these symptoms
Abnormality of coagulation
0001928
Abnormality of the tongue
Abnormal tongue
Tongue abnormality

[ more ]

0000157
Brushfield spots
0001088
Glaucoma
0000501
Primary adrenal insufficiency

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 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.[5][1]

Yes. Clinical genetic testing is available for the twelve genes known to cause Zellweger syndrome.[1] 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).[5][1][6]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Zellweger syndrome. Click on the link to view a sample search on this topic.

            References

            1. Steven J Steinberg, PhD, Gerald V Raymond, MD, Nancy E Braverman, MS, MD, and Ann B Moser, BA. Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum. GeneReviews. May 2012; https://www.ncbi.nlm.nih.gov/books/NBK1448/.
            2. Zellweger spectrum. Genetics Home Reference. June 2015; https://ghr.nlm.nih.gov/condition/zellweger-spectrum.
            3. Zellweger syndrome. Orphanet. December 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=912.
            4. Zellweger syndrome. Orphanet. January 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=912. Accessed 12/29/2011.
            5. Zellweger Spectrum Disorders. NORD. September 15, 2008; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/363/viewAbstract.
            6. NINDS Zellweger Syndrome Information Page. National Institute of Neurological Disorders and Stroke. October 2012; https://www.ninds.nih.gov/disorders/zellweger/zellweger.htm.

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