Peroxisomal biogenesis disorder-Zellweger spectrum disorder (PBD-ZSD) is a rare, genetic condition caused by the loss of peroxisome function. Previously, PBD-ZSD was thought to be three separate diseases known by various names, so you may hear other names used for this disorder. It is now believed that PBD-ZSD is 1 disease with a range of symptoms and severity.
Peroxisomes are important parts of cells in the body that are responsible for many key metabolic functions, such as breaking down fats, including very-long–chain fatty acids (also called VLCFA), and other chemicals, and getting rid of waste so that the body can function properly.
In people with PBD-ZSD, a permanent change in one of the PEX genes (the set of genes that controls peroxisomes) leads to less or no peroxisome function. If peroxisomes are not working correctly, cells can’t perform their normal functions, which changes the body’s usual routine and leads to many problems over time.
The role of peroxisomes in the liver
Peroxisomes help produce bile acids, which are important to help the liver function correctly and eliminate waste from the body.
In PBD-ZSD, non-working peroxisomes cannot produce healthy bile acids; instead, toxic bile acids get trapped in the liver, cause damage, and the liver cannot function properly. These toxic bile acids are known as:
- Dihydroxycholestanoic acid (DHCA)
- Trihydroxycholestanoic acid (THCA)
The spectrum of severity
PBD-ZSD is a set of 3 disorders that form a spectrum of disease that ranges from mild to moderate to severe. PDB-ZSD can affect people differently depending partly on how old they are when symptoms first start to appear.
However, it can be difficult to tell 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.
The 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 do not function properly. When peroxisomes only partially work—or donʼt work at all—bile acids are not made correctly. Peroxisomes are also needed throughout the body, so 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 to 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 cirrhosis (scarring of the liver).
How to know if your child 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 in which symptoms first appear, how many peroxisomes a person has, and which organs are affected.
One of the most common symptoms of patients with PBD-ZSD 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, or K)
Pale, foul-smelling stools
Dark (tea-colored) urine
Enlarged liver or spleen
Elevated liver enzymes