How is Zellweger syndrome diagnosed?

Zellweger syndrome is diagnosed through a combination of clinical findings, laboratory tests, and imaging studies. Here are the key diagnostic steps:

1. Clinical Evaluation:

- Physical examination: The doctor will look for characteristic physical features of Zellweger syndrome, such as a distinctive facial appearance with a high forehead, wide-set eyes, a broad nasal bridge, and a small chin. Other features may include hypotonia (low muscle tone), seizures, developmental delays, liver and kidney problems, and vision and hearing difficulties.

2. Laboratory Tests:

- Blood tests: Blood tests may reveal elevated levels of very long-chain fatty acids (VLCFAs) due to the impaired breakdown of these fats. Low levels of dolichol, a lipid molecule involved in protein glycosylation, may also be found.

- Genetic testing: Genetic testing can identify mutations in the genes involved in Zellweger syndrome, including PEX1, PEX2, PEX3, PEX5, PEX6, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26, and PEX31. Molecular analysis of these genes can confirm the diagnosis.

3. Imaging Studies:

- Magnetic resonance imaging (MRI) of the brain: MRI can reveal abnormalities in the brain structure, such as agenesis of the corpus callosum (ACC), which is a thick band of nerve fibers connecting the two hemispheres of the brain. ACC agenesis is a common finding in Zellweger syndrome.

- Computed tomography (CT) scan of the abdomen: A CT scan can show abnormalities in the liver, such as enlargement or fatty infiltration, which are often seen in Zellweger syndrome.

4. Prenatal Diagnosis:

- Prenatal testing can be performed if Zellweger syndrome is suspected in a fetus. This can be done through chorionic villus sampling (CVS) or amniocentesis, where a sample of the placental tissue or amniotic fluid is analyzed for genetic mutations associated with the condition.

It's important to note that a diagnosis of Zellweger syndrome is made based on a combination of these findings and may involve a multidisciplinary team of healthcare professionals, including geneticists, neonatologists, neurologists, and other specialists.