PBD-ZSD can affect how peroxisomes work
Peroxisomes are important parts of cells.
They are responsible for several key functions in the body including:
Breaking down fats
Peroxisomes help break down fats, especially very-long-chain fatty acids (VLCFAs), which are important for energy
Getting rid of waste
Peroxisomes help clean up waste and toxins in cells, so the body can function properly
In people with PBD-ZSD, a change in a gene called PEX causes peroxisomes to either work poorly or not at all. This means that peroxisomes cannot do their important jobs. This can lead to problems in the body over time.
One condition, multiple names: PBD-ZSD was once thought to be 3 separate diseases, so you may hear different names for it. However, it is now understood to be 1 disease with a range of symptoms and severity.
The important role of peroxisomes in liver health
Peroxisomes are important parts of cells in the liver that help produce bile acids. Bile acids are essential for helping the liver work properly and getting rid of waste from the body.
Since people with PBD-ZSD have peroxisomes that don’t work as they should, they cannot make the healthy bile acids they need. Instead, toxic bile acids, dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA) build up in the liver. The buildup of these toxins can cause damage and makes it harder for the liver to work properly.
The spectrum of severity
PBD-ZSD is a spectrum of 3 related disorders. A spectrum means that something can show a range of differences. In the case of PBD-ZSD, the spectrum ranges from mild to severe. The severity of the condition can vary from person to person, and how it affects someone may depend partly on their age when symptoms first appear.
Zellweger Spectrum Age when symptoms first appear
0 TO 1 YEAR
(Zellweger syndrome)
4 to 10 YEARS
(formerly neonatal adrenoleukodystrophy)
10 to 20 YEARS
(formerly infantile Refsum disease)
SEVERE
It can be difficult to tell exactly where a person’s disease falls on the spectrum because of many contributing factors, such as:
- How old someone is when symptoms first start to appear
- How many functioning peroxisomes a person has
- How quickly the disease progresses
Underlying cause of PBD-ZSD
PBD-ZSD is caused by a defect in one of the PEX genes. When there is a defect in one of these genes, peroxisomes only partially work—or don’t work at all—resulting in bile acids that are not made correctly. Peroxisomes are also needed throughout the body, and if they are not working correctly, multiple organs and body systems can be negatively affected.
So, why are bile acids important?
Bile acids are a key component of bile, which is produced by the liver to help digest and absorb dietary fats, vitamins, and other nutrients. Bile also helps remove excess cholesterol, bilirubin, waste, and toxins from the body.
When bile acids are not made correctly, atypical bile acids are formed. These atypical bile acids, along with toxins and waste, get trapped in the liver. This toxic buildup stops or slows the flow of bile from the liver, a condition called cholestasis, which can lead to inflammation, liver damage, and scarring of the liver (cirrhosis).
How to know if you or your
loved one has liver involvement
While liver involvement is almost universal with PBD-ZSD, signs can vary from person to person and affect different parts of the body.
Symptoms of PBD-ZSD vary depending on the age at which signs first appear, how many peroxisomes a person has, and which organs are affected.
One of the most common signs of PBD-ZSD in patients who show signs of liver involvement is prolonged jaundice—a yellowish color to the skin or white part of the eyes—that lasts more than 2 weeks.
Other signs and symptoms of liver involvement include:
Poor growth (not meeting weight or height milestones for age)
Vitamin deficiencies (vitamins A, D, E, K)
Pale, foul-smelling stools
Dark (tea-colored) urine
Enlarged liver or spleen
Elevated liver enzymes
Diagnosing PBD-ZSD
People living with PBD-ZSD can fall on the mild, moderate, or severe part of the spectrum, with symptoms appearing as early as infancy. If you notice your child exhibiting any of the symptoms mentioned above, it’s important for your child’s doctor to run tests in order to diagnose the cause.
Talk to a health care provider to learn more about PBD-ZSD.
