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What do you need to know about your child’s Zellweger spectrum disorder (ZSD)?

Defining ZSDs

It is 1 disease, but it has a spectrum of severity

Until recently, ZSDs were viewed as 3 separate diseases, but we now know they are a set of disorders that form a spectrum, or continuum, of 1 disease. This spectrum can range from mild (infantile Refsum disease, or IRD), to moderate (neonatal adrenoleukodystrophy, or NALD), to severe (Zellweger syndrome, or ZS).

Image of a human silhouette standing in front of a thick bar that ranges in shades of the color orange to represent the spectrum of disease by the 3 subgroups: IRD, NALD, ZS

ZSDs are also known as peroxisome biogenesis disorders (PBDs). These disorders are caused by a loss of function in important parts of your cells called “peroxisomes,” which can affect many parts of the body--from the eyes to the liver. Learn more about how it works here.

As a spectrum, ZSDs will affect each patient differently. How the disorders affect patients depends on their age when ZSD symptoms first start to appear.

No matter where someone is on the Zellweger spectrum, the impact is serious and lifelong, and it needs to be monitored consistently.

You are your child’s Champion—know how their ZSD is affecting them

What to watch out for when your child has a ZSD

How and when ZSDs affect different parts of the body can vary widely

ZSDs affect each person differently. Monitor your child for any changes to his/her symptoms, so you and your child’s healthcare team can provide timely care.

Not all changes to your child’s health can be easily noticed, so going to routine checkups with different specialists is very important

How do ZSDs affect different body systems and functions?

Nutrition and growth

Hearing

Vision

Neurological

Liver

Kidney

Hormone levels

Bone

Teeth

Control of movement

Children with ZSDs may experience malabsorption

Signs and symptoms

Poor growth
Feeding problems
Deficiency in fat-soluble vitamins (which dissolve and are stored in fat in the body)

Background

Low levels of bile acids lead to poor absorption of nutrients into the bloodstream and a deficiency in fat-soluble vitamins.
Currently, there is no specific diet recommendation for people with ZSDs.
Children with ZSDs are often very picky about what they will eat.
Severely reduced muscle tone often contributes to feeding problems. In more severe cases, some infants may be unable able to suck or swallow.

You are your child’s Champion—learn how to best manage their condition

Some degree of hearing loss is common in children with ZSDs

Signs and symptoms

Hearing loss
Abnormal shape of ears
Ears rotated further back

Background

Deafness is nearly universal in children.
In infants, deafness is typical but not always noticed right away.
Teens and adults often have some form of hearing loss.
Hearing should be evaluated every year.

You are your child’s Champion—learn how to best manage their condition

Some degree of vision loss is very common in people with ZSDs

Signs and symptoms

Vision loss
Spots on or around the iris
Cataracts (when the lens of the eye is cloudy)

Background

Vision loss from damage to the retina (the tissue at the back of the eye) is among the most common symptoms in people with ZSDs.
Cataracts can blur vision but are less common.
Glaucoma and other issues with the retina may develop in severe cases.

You are your child’s Champion—learn how to best manage their condition

ZSDs often affect the nervous system

Signs and symptoms

Developmental delay in mental and/or physical abilities
Seizures, most often seen in newborns
Numbness, muscle weakness, or tingling, often in hands or feet
Inflammation of a brain region called the cerebellum

Background

Improper development of the white matter in the brain (leukodystrophy) in children with ZSDs results in nerve damage, potentially affecting their development.
Damage to the nerves that send information from the brain to the rest of the body (peripheral neuropathy) can often cause numbness or weakness in the hands and/or feet.
Walking abnormality is the main neurological complication in adults with ZSDs.
In people with mild forms of ZSDs, nerve damage to the muscles, skin, and internal organs usually begins during adolescence.

You are your child’s Champion—learn how to best manage their condition

Liver injury is almost universal

Signs and symptoms

Yellowing of eyes and skin (jaundice)
Enlarged liver (hepatomegaly)
Inflammation (cirrhosis)
Scarring (fibrosis)

You may notice jaundice, but routine monitoring with liver function tests (LFTs)—which are done with a blood sample at the doctor’s office—and bile acid analysis are the best ways to know the condition of your child’s liver.

Background

In ZSDs, a genetic defect causes a reduction or absence of an important component of many cells called “peroxisomes.”
A large number of peroxisomes can be found in the liver, helping with the production of bile acids, which are important for health.
When the liver lacks peroxisomes and cannot produce normal essential bile acids, abnormal toxic substances are produced in their place that cannot flow properly from the liver.
These toxic substances build up in the liver, which can lead to scarring of the liver and liver failure.
Unmanaged, progressive liver disease may increase the chance of having poorer disease outcomes.
LFTs help monitor liver health by checking the blood for liver enzymes.

You are your child’s Champion—learn how to best manage their condition

The kidneys may be affected by ZSDs

Signs and symptoms

Kidney stones
Kidney cysts (abnormal sacs)
Kidney failure

Background

Kidney problems are more common in children 4 years of age and older.
Older patients with ZSDs should be monitored for hyperoxaluria, a condition of the kidneys that leads to recurring bladder and kidney stones.
Kidney failure may also result in older patients and should be monitored.
Infants with ZSDs may have abnormally large kidneys.

You are your child’s Champion—learn how to best manage their condition

People with ZSDs may have low levels of certain hormones

Signs and symptoms

Muscle pain
Joint pain
Vomiting
Low levels of sodium
Low blood pressure
Darkening of your skin (hyperpigmentation)

Background

Poor function in the adrenal glands, small organs that produce hormones, is common and may be underdiagnosed in people with ZSDs.
Hormone imbalances are fairly common in people with ZSDs but may be overlooked.
Hormone imbalances do not always cause symptoms, highlighting the importance of screenings at routine doctor follow-ups.

You are your child’s Champion—learn how to best manage their condition

People with ZSDs may have bone abnormalities

Signs and symptoms

Unusual spots on the ends of bones (ie, ankles, fingers)
Low bone density

Background

X-rays may show abnormal spots around the growth plates (the growing tissue near the ends of long bones in children and adolescents) in severe cases. Your doctor may call this condition “chondrodysplasia punctata.”
Decreased bone density has been linked to worsening of disease.
Fractures can occur at random. A dual-energy x-ray absorptiometry scan is a bone density scan that can assess bone strength and risk of a fracture.

You are your child’s Champion—learn how to best manage their condition

ZSDs often affect the teeth

Signs and symptoms

Enamel abnormalities
Teeth slow to emerge
Small, poorly formed teeth
Orange-/yellow-colored teeth

Background

Dental examinations are recommended every 6 months.
Management of abnormalities in children’s permanent teeth depends on the severity of the problem.

You are your child’s Champion—learn how to best manage their condition

The ability to control movement is often affected by ZSDs

Signs and symptoms

Poor movement
Walking abnormality
Low muscle tone and strength

Background

Delays in meeting developmental milestones such as lacking head control or responding to sights or sounds.

You are your child’s Champion—learn how to best manage their condition

Uncover the underlying cause of ZSDs

ZSDs can be confusing and overwhelming, but having all the facts can empower you to best support your child or loved one.

Click through the slideshow below to learn how ZSDs develop, and what you can expect when caring for a child with this disease.

Illustration of a human cell with a focus on the peroxisome. The loss of peroxisome function causes Zellweger spectrum disorders.�

Illustration displaying normal peroxisome function.�

Illustration displaying how an alteration in the PEX gene family leads to a loss of normal peroxisome function in Zellweger spectrum disorders.�

Icons represent the many body systems affected by Zellweger spectrum disorders, including the eyes, liver, and nervous system.�

Illustration of a healthy liver, in which normal bile acids are present to eliminate toxins from the body and help ensure proper liver function.�

Illustration of a damaged liver in which waste and toxins have accumulated due to the lack of normal bile acids and working peroxisomes in the liver.�

Illustration of a human silhouette with icons representing the various bodily effects of Zellweger spectrum disorders, including neurological problems, delayed growth, hearing and vision loss, and skeletal abnormalities�.

Illustration of a human silhouette standing in front of a bar ranging in shade of the color orange. This represents the spectrum of disease in Zellweger spectrum disorders, ranging from less to more severe.�

Illustration of different doctors standing together as a team portrays the importance of having a diverse team of specialists to best manage a Zellweger spectrum disorder.�

ZSDs are a set of genetic diseases that are caused by a loss of peroxisome function. Peroxisomes are important parts of your cells that are responsible for breaking down fats and chemicals, and getting rid of waste so that your body can function properly.

A family of genes called PEX provides the instructions for how to correctly assemble peroxisomes. When peroxisomes are made correctly, they ensure that the chemical reactions in your cells are working properly and that your body is in good health.

In people with ZSDs, a permanent alteration in the PEX gene family leads to a loss of peroxisome function. If peroxisomes are not working, cells can no longer maintain their normal functions, altering the body’s usual routine and leading to many problems over time.

Because peroxisomes are present in almost all cells, loss of peroxisome function can cause harmful consequences to the entire body. Many key organs, including the brain, eyes, and liver, cannot function properly.

Let’s look at an example of how the absence of working peroxisomes can affect how an organ works. A large number of peroxisomes can be found in the liver, aiding in the production of bile and bile acids. Bile acids help to absorb fats and vitamins from the food you eat while eliminating cholesterol, waste, and other toxins from your body.

Because of the reduction or absence of working peroxisomes in the liver, bile acids cannot be made correctly. Toxic components, such as atypical bile acids and waste, get trapped in the liver, resulting in a condition called cholestasis. This toxic buildup can lead to inflammation, liver damage, and cirrhosis, which is when the liver becomes scarred and unable to function properly.

Peroxisomes play a similar role in different organ systems, so their abnormal function can lead to a variety of symptoms. People with ZSDs may experience multisystemic complications including neurological problems and seizures, delayed growth and development, hearing and vision loss, poor muscle tone, and skeletal and dental abnormalities.

There is no way to know exactly where a person’s disease falls on the spectrum. There are many factors that contribute to how the disease will affect someone, including the age at which their symptoms first start to appear, the number of functioning peroxisomes they have, and the rate at which the disease progresses.

Due to their multisystemic nature, ZSDs require a diverse team of specialists to help monitor and manage the symptoms of disease. Talk to your healthcare team about routine checkups and the best ways to support your child or loved one with ZSDs.

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