Zellweger spectrum disorder
Zellweger spectrum disorder is a condition that affects many parts of the body, caused by the impaired formation of peroxisomes.
Overview
Zellweger spectrum disorder is a condition that affects many parts of the body. Cases of Zellweger spectrum disorder are often categorized as severe, intermediate, or mild.
Individuals with severe Zellweger spectrum disorder usually have signs and symptoms at birth, which worsen over time. These infants experience weak muscle tone (hypotonia), feeding problems, hearing and vision loss, and seizures. These problems are caused by reduced 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. Reduced myelin (demyelination) leads to loss of white matter (leukodystrophy).
Children with severe Zellweger spectrum disorder also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys, and their liver or spleen may be enlarged. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanelles) and characteristic bone spots known as chondrodysplasia punctata that can be seen on x-ray. Affected individuals can have eye abnormalities, including clouding of the lenses of the eyes (cataracts) or involuntary, side-to-side movements of the eyes (nystagmus). Severe Zellweger spectrum disorder involves distinctive facial features, including a flattened face, epicanthal folds, high forehead, and widely spaced eyes (hypertelorism). Children with severe Zellweger spectrum disorder typically do not survive beyond the first year of life.
People with intermediate or mild Zellweger spectrum disorder have more variable features that progress more slowly than those with the severe form. Affected children usually do not develop signs and symptoms of the disease until late infancy or early childhood. Children with these intermediate and mild forms often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability.
Frequency
Zellweger spectrum disorder is estimated to occur in 1 in 50,000 individuals.
Causes
Variants in at least 12 genes have been found to cause Zellweger spectrum disorder. 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.
Variants in the genes that cause Zellweger spectrum disorder prevent peroxisomes from forming normally. Diseases that disrupt the formation of peroxisomes, including Zellweger spectrum disorder, are called peroxisome biogenesis disorders. If the production of peroxisomes is altered, these structures cannot perform their usual functions. The signs and symptoms of severe Zellweger spectrum disorder are due to the absence of functional peroxisomes within cells. Intermediate and mild Zellweger spectrum disorder are caused by variants that allow some peroxisomes to form.
Variants in the PEX1 gene are the most common cause of Zellweger spectrum disorder and are found in nearly 70 percent of affected individuals.
Gene associated with Zellweger spectrum disorder
- PEX1
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Cerebrohepatorenal syndrome
- PBD, ZSS
- PBD-ZSD
- Peroxisome biogenesis disorders, Zellweger syndrome spectrum
- Zellweger spectrum
- Zellweger syndrome spectrum
- ZSD