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Zellweger syndrome: causes, symptoms and treatment

Zellweger syndrome: causes, symptoms and treatment

February 8, 2023

Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease and hyperpipecular acidemia are all part of the Zellweger spectrum disorders. This set of diseases affects in different degrees the biogenesis of the cellular organelle called "peroxisome", which can cause premature death.

In this article we will describe the main causes and symptoms of Zellweger syndrome , the most serious variant of peroxisome biogenesis disorders. In the other alterations of this group the signs are similar but have a lower intensity.

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What is Zellweger syndrome?

Zellweger syndrome is a disease that affects functions such as muscle tone or visual and auditory perception, as well as the tissues of the bones or organs such as the heart and liver. Its origin has been related to the presence of mutations in certain genes that are transmitted by autosomal recessive inheritance.


Children diagnosed with Zellweger syndrome tend to die before the end of the first year of life . Many of them die before 6 months as a result of alterations in the liver or in the respiratory and gastrointestinal systems. However, people with mild variants can live to adulthood.

Currently there is no known treatment that resolves the deep changes that cause Zellweger syndrome, so the management of this disease is symptomatic.

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Zellweger's spectrum disorders

It is now known that Zellweger syndrome is part of a set of diseases that have the same genetic cause: peroxisome biogenesis disorders (organelles that play a role in the functioning of enzymes), also known as "Zellweger spectrum disorders".


Classic Zellweger syndrome is the most serious variant of peroxisome biogenesis disorders, while cases of intermediate severity are termed "neonatal adrenoleukodystrophy" and milder cases such as "infantile Refsum disease". Hyperpipecular acidemia is also a low intensity form of this alteration.

Previously it was believed that these alterations were independent of each other. Zellweger's syndrome was the first to be described, in 1964; the identification of the rest of the spectrum disorders occurred in the following decades.

Symptoms and main signs

In the Zellweger syndrome the alteration in the biogenesis of the peroxisome causes them to occur neurological deficits that cause a wide variety of symptoms in different systems and bodily functions. In this sense, the signs of the disorder are related to brain development, and particularly to neuronal migration and positioning.


Among the symptoms and the most frequent and characteristic signs of Zellweger syndrome are the following:

  • Decreased muscle tone (hypotonia)
  • Convulsive crisis
  • Loss of auditory sensory abilities
  • Alterations of the ocular system and sight (nystagmus, cataracts, glaucoma)
  • Difficulties in eating food
  • Impairment of normal physical development
  • Presence of characteristic facial features (flat face, high forehead, broad nose ...)
  • Presence of other morphological alterations (microcephaly or macrocephaly, folds in the neck ...)
  • Abnormalities in the structure of bones, especially chondrodysplasia punctata (cartilage calcification)
  • Increased risk of developing disorders of the heart, liver and kidneys
  • Respiratory disorders such as apnea
  • Appearance of cysts in the liver and kidneys
  • Increase in the size of the liver (hepatomegaly)
  • Detection of abnormalities in the encephalographic record (EEG)
  • General alteration of the functioning of the nervous system
  • Hypomyelination of axonal fibers of the central nervous system

Causes of this disease

Zellweger syndrome has been linked to the presence of mutations in at least 12 genes; Although there may be alterations in more than one of them, it is enough that there is an altered gene so that the symptoms that we have described in the previous section appear. In approximately in 70% of the cases the mutation is located in the PEX1 gene .

The disease is transmitted through an autosomal recessive inheritance mechanism.This means that a person has to inherit a mutated copy of the gene from each of their parents to present the typical symptoms of Zellweger syndrome; when both parents carry the mutant gene there is a 25% risk of developing the disease.

These genes are related to peroxisome synthesis and function , habitual structures in the cells of organs like the liver that are fundamental for the metabolization of fatty acids, for the elimination of residues and for the development of the brain in general. Mutations alter the gene expression of peroxisome.

Treatment and management

To date, no effective treatment for Zellweger syndrome is known, despite the improved understanding of the genetic, molecular and biochemical alterations associated with the disease. That is why The therapies that are applied in these cases are basically symptomatic and adapt to the signs of each specific case.

The problems to eat properly are a sign with a special relevance due to the risk of malnutrition that it supposes. In these cases it may be necessary to apply a feeding probe to minimize interference in the child's development.

The treatment of Zellweger syndrome is carried out through multidisciplinary teams that can include professionals from pediatrics, neurology , of orthopedics, ophthalmology, audiology and surgery, among other branches of medical science.


Zellweger Syndrome | USMLE Step 1 Peroxisome Disorder (February 2023).


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