Overview of Zellweger Syndrome

Zellweger syndrome falls into a group of conditions called peroxisome biogenesis disorders (PBD). These conditions are caused by mutations in one of your child’s PEX genes that code for the creation of tiny structures inside your cells called peroxisomes.

Peroxisomes break down toxic substances and create lipids, which are fat molecules. They’re required for brain development and are important for your:

• eyes
• liver
• kidney
• bones

Zellweger syndrome is a recessive condition that only develops if your child receives an associated gene from both parents. For this reason, it’s relatively rare and is only estimated to occur in about 1 in 50,000 live births in the United States.

PBDs are divided into two main categories.

1. Zellweger spectrum disorder (ZSD)
2. Rhizomelic chondrodysplasia punctata spectrum

ZSD further divides into three subcategories that vary in severity:

• Zellweger syndrome: Zellweger syndrome is the most severe form. Most children pass away before their first birthday.
• Neonatal adrenoleukodystrophy: Neonatal adrenoleukodystrophy is the intermediate form of ZSD. Symptoms like hearing loss and vision loss onset from birth to childhood, and most children pass away before the age of 3 years.
• Infantile Refsum disease: Infantile Refsum disease is the mildest form of ZSD. Most people survive 5–13 years if symptoms start in infancy and 30–40 years if symptoms develop later.

About 80 babies are born with ZSD in the United States each year.

Many of the symptoms of Zellweger syndrome are present from birth. Signs and symptoms of the disorder may include:

• particular facial features, such as:
  • underdeveloped eyebrow ridges
  • wideset eyes
  • high forehead
• floppy muscle tone
• poor feeding
• difficulty gaining weight
• failing to grow as expected
• neurological complications, such as:
  • frequent seizures
  • poor or absent reflexes
  • intellectual disability
  • development delays
  • trouble with movement
• cataracts
• involuntary eye movements
• jaundice
• severe liver disease
• cysts on the kidneys

Children with Zellweger syndrome usually pass away before the age of 1 year due to severe liver disease. Other complications can include:

• gastrointestinal bleeding
• pneumonia that can lead to septic shock
• respiratory disease
• frequent or severe infections
• an enlarged liver or spleen

Zellweger syndrome may be diagnosed shortly after birth or before birth.

If both parents carry a known gene associated with Zellweger syndrome, your doctor may screen your child while they’re still in the womb using imaging or a blood test.

More commonly, a child will receive a diagnosis of Zellweger syndrome shortly after birth. Tests your doctor may use to diagnose it include:

• blood tests to look for elevated levels of very-long-chain fatty acids and other markers
• genetic tests
• imaging like ultrasound or brain MRI to monitor your child’s organ development
• urine tests

Zellweger syndrome doesn’t have a cure. Treatment aims to reduce your child’s symptoms and might include:

• vitamin supplements
• surgery
• treatment to correct hearing and vision problems
• medications like antiseizure drugs
• use of a feeding tube

Children with Zeweger syndrome generally pass away within their first year of life due to progressive liver disease. People with milder forms of ZSD may live into adulthood.

There’s no way to prevent Zellweger syndrome. If you have a family history of the disease, you may want to consider genetic counseling to learn if you carry an associated gene.

Learn more about genetic testing.

Your child’s healthcare team can advise you on how to best help your child. Although Zellweger syndrome doesn’t have a cure, treatments such as pain relievers and a breathing tube can help ease their symptoms.

You may also ask your child’s doctor about potential clinical trials for which your child may be eligible to help researchers learn more about the disease.

Knowing that you may lose your child can be very difficult. It’s normal to feel shocked, overwhelmed, or angry. Some ways you may be able to make this challenging time easier include:

• taking care of yourself by sleeping and eating well
• trying to develop a routine
• surrounding yourself with supportive friends and family
• considering attending support groups or counseling
• thinking of ways you can honor your child if they pass away

You may also find some of the following resources helpful:

• current clinical trials from the National Library of Medicine
• information and support from the Global Foundation of Peroxisomal Disorders
• support for parents of deaf and blind children from the National Center on Deafblindness
• resources for those grieving the death or impending death of a child from The Miss Foundation

Here are some frequently asked questions people have about Zellweger syndrome.

How common is Zellweger syndrome?

Zellweger spectrum disorder occurs in about 1 in 50,000 live births in the United States. It seems to be particularly common in the Canadian province of Quebec, occurring in about 1 in 12,000 births.

Can Zellweger syndrome be diagnosed before birth?

Zellweger syndrome can be diagnosed before birth with genetic screening. Advances in imaging have also made it possible to diagnose Zellweger syndrome with an MRI in some cases.

Zellweger syndrome is a severe genetic condition caused by a mutation in one of your child’s PEX genes. Most children with Zellweger’s syndrome pass away before the age of 1 year.

Finding out your child has Zellweger syndrome can be very stressful. Although there’s no cure, medications and other supportive treatments can ease your child’s symptoms.