Zellweger Syndrome: Causes, Symptoms And Treatment
Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and hyperpipecolic acidemia are part of the Zellweger spectrum disorders. This set of diseases affects to different degrees the biogenesis of the cellular organelle called “peroxisome”, and can cause premature death.
In this article we will describe The main causes and symptoms of Zellweger syndrome, the most severe variant of peroxisome biogenesis disorders. In the rest of the alterations in this group the signs are similar but have a lower intensity.
Zellweger syndrome is a disease that affects functions such as muscle tone or visual and auditory perception, as well as bone tissues 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 the respiratory and gastrointestinal systems. However, people with mild variants can live to adulthood.
Currently, there is no known treatment that resolves the profound alterations that cause Zellweger syndrome, so the management of this disease is symptomatic.
Zellweger spectrum disorders
It is currently known that Zellweger syndrome is part of a group 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 severe variant of peroxisome biogenesis disorders, while cases of intermediate severity are called “neonatal adrenoleukodystrophy” and the mildest cases are called “infantile Refsum disease.” Hyperpipecolic acidemia is also a low-intensity form of this disorder.
It was previously believed that these alterations were independent of each other. Zellweger syndrome was the first to be described, in 1964; The identification of the rest of the spectrum disorders occurred in the following decades.
Main symptoms and signs
In Zellweger syndrome, the alteration in peroxisome biogenesis causes the production of neurological deficits that cause a wide variety of symptoms in different body systems and functions. In this sense, the signs of the disorder are related to brain development, and particularly to neuronal migration and positioning.
Among the most frequent and characteristic symptoms and signs of Zellweger syndrome we find the following:
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 for there to be an altered gene for the symptoms that we have described in the previous section to appear. In approximately In 70% of 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 the synthesis and function of the peroxisome, common structures in the cells of organs such as the liver that are essential for the metabolization of fatty acids, for the elimination of waste and for brain development in general. Mutations alter peroxisome gene expression.
Treatment and management
To date, there is still no known effective treatment for Zellweger syndrome, despite improved understanding of the genetic, molecular and biochemical alterations that are associated with the disease. That is why The therapies applied in these cases are basically symptomatic. and adapt to the signs of each specific case.
Problems eating food adequately are a sign with special relevance due to the risk of malnutrition it poses. In these cases it may be necessary to apply a feeding tube to minimize interference with the child’s development.
The treatment of Zellweger syndrome is carried out through multidisciplinary teams that can include professionals from pediatrics, neurology orthopedics, ophthalmology, audiology and surgery, among other branches of medical science.
