Zellweger Syndrome

Zellweger Syndrome

Zellweger syndrome is a genetic disorder passed from parents to children. It disrupts cellular function and causes serious problems soon after birth. Newborns can have brain, liver, and kidney problems, as well as difficulty feeding or moving. Unfortunately, there is no cure or effective treatment, and infants with the disease usually don’t live past their first year of life.

Zellweger Spectrum Disorders (ZSDs)

Zellweger spectrum disorders, also known as peroxisomal biogenesis disorders, impact peroxisomes—cellular structures vital for numerous bodily functions. The spectrum includes:

Heimler Syndrome

• Characteristics: Late infancy or early childhood hearing loss and dental issues.

Infantile Refsum Disease

• Characteristics: Muscle movement problems and developmental delays in babies.

Neonatal Adrenoleukodystrophy

• Characteristics: Hearing and vision loss, along with issues affecting the brain, spine, and muscles in infants.

Who is Affected by Zellweger Syndrome?

Zellweger syndrome arises from specific gene mutations and follows an autosomal recessive inheritance pattern, meaning both parents must pass on a copy of the mutated gene for a child to develop the disorder. If both parents are carriers of the mutated gene, their offspring have:

• A 50% chance of becoming carriers like the parents.
• A 25% chance of developing the disease.

Prevalence of Zellweger Syndrome

Zellweger syndrome is a rare condition, and when combined with other disorders within the Zellweger spectrum, they affect approximately 1 in 50,000 to 1 in 75,000 newborns.

Causes and Symptoms

Zellweger syndrome arises due to mutations in any of the 12 PEX genes, with the PEX1 gene accounting for most ZS cases. These genes regulate peroxisomes, crucial for normal cellular functioning as they aid in the breakdown of toxins and fats. Peroxisomes play a pivotal role in the development of various organs, including the bones, brain, eyes, heart, kidneys, liver, and nerves.

Common Symptoms

• Facial Features: Broad nose bridge, epicanthal folds (skin folds at the inner corners of the eyes), flattened face, high forehead, underdeveloped eyebrow ridges, wide-set eyes.
• Other Symptoms: Difficulty with feeding, an enlarged liver and/or spleen, gastrointestinal bleeding, hearing and vision problems, jaundice (yellowing of the skin and eyes due to liver dysfunction), seizures, and underdeveloped muscles leading to movement difficulties.

Diagnosis and Testing

At Birth

• Characteristic Facial Features: Observation of distinctive facial characteristics can prompt initial suspicion.

Confirmatory Tests

• Blood and Urine Tests: Elevated levels of specific substances in blood or urine, such as fat molecules, may indicate ZS.
• Imaging Tests: Ultrasound examinations assess the size and function of organs like the liver and kidneys. Brain MRI scans are also conducted to aid in diagnosis.
• Genetic Tests: Blood tests can determine the presence of mutated PEX genes.

Prenatal Diagnosis

If both parents are carriers of mutated PEX genes and there is a risk of ZS in the fetus, healthcare providers may conduct blood or imaging tests to assess the condition while the baby is still in the womb.

Management and Treatment

There is currently no cure for Zellweger syndrome. Some therapies can alleviate symptoms, but none address the underlying cause of the disorder. For example, a feeding tube may help a baby struggling with feeding, but they won’t be able to eat normally in the future.

Prevention

Zellweger syndrome cannot be prevented. However, individuals with a family history of the condition may consider genetic counseling to assess the risk of passing the disease to their offspring.

Outlook/Prognosis

Babies with Zellweger syndrome usually do not survive beyond their first year of life. Other disorders within the Zellweger spectrum generally have more favorable prognoses, with children with Refsum or Heimler syndromes potentially living into adulthood.

Living With Zellweger Syndrome

For carriers of Zellweger syndrome-associated gene mutations, genetic counseling can provide guidance in evaluating the risks associated with having children. If a child is born with ZS, a team of neonatologists can assist parents in selecting the appropriate care plan for their child.