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The Zellweger spectrum is a group of conditions that have overlapping signs and symptoms and affect many parts of the body. This group of disorders includes Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease. These conditions were once thought to be distinct disorders but are now considered to be part of the same disease spectrum. Zellweger syndrome is the most severe form of the Zellweger spectrum, NALD is intermediate in severity, and infantile Refsum disease is the least severe form. In some cases, it can be difficult to distinguish between the three conditions that make up the Zellweger spectrum.
Individuals with Zellweger syndrome develop signs and symptoms of the condition during the newborn period. These infants experience weak muscle tone (hypotonia), feeding problems, hearing loss, vision loss, and seizures. These problems are caused by the degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter. Destruction of the myelin (demyelination) leads to loss of white matter (leukodystrophy). Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanels) and characteristic bone spots known as chondrodysplasia punctata that can be seen with an x-ray. Affected individuals have distinctive facial features, including a flattened face, broad nasal bridge, and high forehead. Children with Zellweger syndrome typically do not survive beyond the first year of life.
People with NALD or infantile Refsum disease have more variable features than those with Zellweger syndrome and usually do not develop signs and symptoms of the disease until late infancy or early childhood. They may have many of the features seen in more severely affected individuals; however, their condition typically progresses more slowly. Children with these less severe conditions often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Most people with NALD survive into childhood, and those with infantile Refsum disease may reach adulthood. In rare cases, individuals at the mildest end of the Zellweger spectrum have developmental delay in childhood and hearing loss or vision problems beginning in adulthood.
The Zellweger spectrum is estimated to occur in 1 in 50,000 individuals.
Mutations in 12 genes have been found to cause the Zellweger spectrum. These genes provide instructions for making a group of proteins known as peroxins, which are essential for the formation and normal functioning of cell structures called peroxisomes. Peroxisomes are sac-like compartments that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production of fats (lipids) used in digestion and in the nervous system. Peroxins assist in the formation (biogenesis) of peroxisomes by producing the membrane that separates the peroxisome from the rest of the cell and by importing enzymes into the peroxisome.
Mutations in the genes that cause the Zellweger spectrum prevent peroxisomes from forming normally. Diseases that disrupt the formation of peroxisomes, including the Zellweger spectrum, are called peroxisome biogenesis disorders. If the production of peroxisomes is altered, these structures cannot perform their usual functions. The signs and symptoms of Zellweger syndrome are due to the absence of functional peroxisomes within cells. NALD and infantile Refsum disease are caused by mutations that allow some peroxisomes to form.
Mutations in the PEX1 gene are the most common cause of the Zellweger spectrum and are found in nearly 70 percent of affected individuals. The other genes associated with the Zellweger spectrum each account for a smaller percentage of cases of this condition.
Changes in these genes are associated with Zellweger spectrum.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of Zellweger spectrum and may include treatment providers.
You might also find information on the diagnosis or management of Zellweger spectrum in Educational resources (http://www.ghr.nlm.nih.gov/condition/zellweger-spectrum/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/zellweger-spectrum/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about Zellweger spectrum helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
acids ; autosomal ; autosomal recessive ; cell ; demyelination ; developmental delay ; digestion ; fatty acids ; gene ; hypotonia ; leukodystrophy ; muscle tone ; neonatal ; nervous system ; peroxisomes ; recessive ; spectrum ; syndrome ; toxic ; white matter
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.