What is PBD-ZSD?

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.

PBD-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

Diagnosing PBD-ZSD

People living with PBD-ZSD can fall into the mild, moderate, or severe side 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. Learn more about available testing for patients to help diagnose PBD-ZSD and/or to see if your child’s liver is being affected.

No-cost Testing Programs

WHAT IS CHOLBAM® (cholic acid) capsules?

CHOLBAM is a prescription medicine. It is a bile acid used for

Treatment of bile acid synthesis disorders (malfunction in the production of bile acid in the liver) due to a lack of a single enzyme responsible for bile acid production.
Treatment (in addition to other treatments) of peroxisomal disorders (a loss of function in important parts of the cell), including Zellweger spectrum disorders, in patients who show signs or symptoms of liver disease, pale stools due to too much fat, or problems resulting from not absorbing certain vitamins (A, D, E, K).

The safety and effectiveness of CHOLBAM on symptoms outside of the liver have not been studied.

IMPORTANT SAFETY INFORMATION

CHOLBAM may not be right for you. Before taking CHOLBAM, tell your doctor about:

All health conditions you may have and any medications you may be taking.
If you are pregnant or plan to become pregnant.
If you are breastfeeding or plan to breastfeed.

What are the possible side effects of CHOLBAM?

Serious Side Effects: You will need to undergo laboratory testing periodically while on treatment to assess liver function. CHOLBAM may worsen liver function. Tell your doctor right away if you experience symptoms associated with worsening of liver function (e.g., skin or the whites of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleeding or bruising occurs more easily than normal, or increased lethargy). Your doctor will decide if you need to discontinue treatment with CHOLBAM.
Most Common Side Effects: Diarrhea, acid reflux that damages the lining of the esophagus, discomfort and fatigue, yellowing of skin or eyes, skin lesion, nausea, abdominal pain, formation of growths in the intestinal tract, urinary tract infection, nerve damage causing change in sensation in extremities.

These are not all the possible side effects of CHOLBAM. Tell your doctor if you have any side effect that bothers you or that does not go away.

You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Mirum Pharmaceuticals at 1-855-MRM-4YOU.

Please see accompanying full Prescribing Information for additional Important Safety Information.