Zellweger Spectrum Syndrome

What are Zellweger syndromes?

Zellweger syndromes are a group of rare, genetic, multisystem disorders. Once thought to be three separate conditions, Zellweger syndrome is now thought to be one disorder classified by severe, moderate and mild forms. The three separate conditions previously identified were neonatal adenoleukodystrophy (NALD), infantile Refusm, and Zellweger spectrum syndrome. Now Zellweger spectrum syndrome is known as the most severe form, NALD is moderate ,and infantile Refusm is the mildest form of this disorder. Individuals with Zellweger spectrum syndrome usually develop severe life threatening conditions during infancy. Those with the mildest form can survive into adulthood. The estimated occurrence of Zellweger spectrum syndrome is 1in 50,000 individuals.

What are the symptoms of Zellweger syndromes?

The symptoms of Zellweger syndromes vary depending on the form of the syndrome present. In Zellweger spectrum syndrome, the most severe form, symptoms appear during infancy. Most individuals will not survive the first year of life. Symptoms include:

• Weak muscle tone
• Hearing and vision loss
• Seizures
• Flattened face
• Broad nasal bridge
• Large forehead
• Abnormally large or small head
• Life threatening dysfunction of heart, lungs, and kidneys
• Enlarged space between the bones of the skull
• Sever dysfunction of brain and spinal cord
• Breathing problems
• Decreased bone density
• Urinary tract and genital abnormalities

Individuals with the moderate and mild forms of this disorder experience varied symptoms that can develop in early childhood to early adulthood, depending on the form they are affected with. These symptoms develop more slowly than Zellweger spectrum syndrome and include:

• Hearing loss
• Vision problems
• Intellectual disability
• Liver problems
• Extreme muscle weakness and lack of muscle tone
• Abnormal tooth enamel

In rare instances, individuals with the mildest form of this disorder may not develop symptoms until later in life. These symptoms include:

• Developmental delays in childhood
• Early adulthood hearing loss and/or vision problems

What causes Zellweger syndromes?

Zellweger syndromes are caused by inherited changes in one of the 13 genes responsible for the creation and function of cell structures known as peroxisomes. These substances are necessary for normal bodily functions, including those in the nervous and digestive systems.

Are there treatment options for Zellweger syndromes?

There is no known cure for Zellweger syndromes. Treatments are instead directed at supportive management of the symptoms of the disorder.  Care is usually managed by a team of specialists including pediatricians, neurologists, surgeons, orthopedic doctors, and hearing and vision specialists. Early intervention is important for individuals with Zellweger syndromes. Treatments include:

• Feeding tubes
• Anti-seizure medications
• Hearing aids or cochlear implants for hearing loss
• Cataract surgery or glasses
• Physical therapy
• Dental care
• Orthopedic devices for bone abnormalities

Where can I find more information about Zellweger syndromes? 

•  The Global Foundation for Peroxisomal Disorders
• U.S. National Library of Medicine
• National Organization of Rare Disorders (NORD)
• NIH