Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and hyperpipecolic acidemia are among the Zellweger spectrum disorders. This collection of diseases affects the biogenesis of the cell organelle called “peroxisome” to varying degrees, which can lead to premature death.
In this article we will describe the main causes and symptoms of Zellweger syndrome, The most serious variant of the disturbances of peroxisome biogenesis. In the other changes in this group, the signs are similar but have a lower intensity.
What is Zellweger Syndrome?
Zellweger syndrome is a disease that affects functions such as muscle tone or visual and auditory perception, as well as bone or organ tissue such as the heart and liver. Its origin is linked to the presence of mutations in certain genes transmitted by autosomal recessive inheritance.
Children diagnosed with Zellweger syndrome they tend to die before the end of the first year of life. Many of them die before 6 months as a result of damage to the liver or the respiratory and gastrointestinal systems. However, people with mild variants can live to adulthood.
Currently, no treatment is known to resolve the profound changes that cause Zellweger syndrome, so management of this disease is symptomatic.
Zellweger spectrum disorders
Zellweger syndrome is now known to be one of a group of diseases that they have the same genetic cause: disorders of peroxisome biogenesis (Organelles that play a role in how enzymes work), also known as “Zellweger spectrum disorders”.
Classical Zellweger syndrome is the most severe variant of the disturbances in peroxisome biogenesis, while cases of intermediate severity are called “neonatal adrenoleukodystrophy” and the milder ones as “infantile Refsum disease”. Hyperpipecolic acidemia is also a low-intensity form of this disorder.
These modifications were previously believed to be independent of each other. Zellweger syndrome was the first to be described, in 1964; the identification of the rest of the spectrum disorders took place in the following decades.
Main symptoms and signs
In Zellweger syndrome, altered peroxisome biogenesis causes their occurrence neurological deficits that cause a wide variety of symptoms in different bodily systems and functions. In this sense, the signs of the disorder are related to the development of the brain, and in particular to neuronal migration and positioning.
The most common and characteristic symptoms and signs of Zellweger syndrome are:
- Decreased muscle tone (hypotonia)
- Loss of hearing sensory abilities
- Eye and visual disturbances (nystagmus, cataracts, glaucoma)
- Difficulty eating
- Impaired normal physical development
- Presence of characteristic facial features (Flattened face, high forehead, wide nose …)
- Presence of other morphological alterations (microcephaly or macrocephaly, folds in the neck …)
- Abnormalities of the bone structure, in particular punctate chondrodysplasia (calcification of the cartilage)
- Increased risk of developing heart, liver and kidney problems
- Respiratory disorders such as apnea
- Appearance of cysts in the liver and kidneys
- Increase in size of the liver (hepatomegaly)
- Detection of abnormalities in the encephalographic record (EEG)
- General impairment of the functioning of the nervous system
- Hypomyelination of axonal fibers of the central nervous system
The 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 for the symptoms that we described in the previous section to appear. in about in 70% of cases, the mutation is localized in the PEX1 gene.
The disease is transmitted by an autosomal recessive transmission mechanism. This means that a person must inherit a mutated copy of the gene from each of their parents to exhibit the typical symptoms of Zellweger syndrome; when both parents carry the mutant gene, they have a 25% risk of developing the disease.
These genes are linked to the synthesis and function of the peroxisome, Structures common in the cells of organs such as the liver, essential for fatty acid metabolism, waste elimination and general brain development. Mutations alter the expression of the peroxisome gene.
Processing and handling
To date, no effective treatment for Zellweger syndrome is known, despite a better understanding of the genetic, molecular and biochemical alterations associated with the disease. that’s why the therapies applied in these cases are mainly symptomatic and adapt to the signs of each particular case.
Problems with good nutrition are a particularly relevant sign for the risk of malnutrition. In these cases, it may be necessary to apply a feeding tube to minimize interference in the development of the offspring.
Treatment of Zellweger syndrome is carried out by multidisciplinary teams who can include professionals from pediatrics, neurology, Orthopedics, ophthalmology, audiology and surgery, among other branches of medical science.