Foundations · Year 1 · from Foundations
Case 3: Zellweger Syndrome (Peroxisome Biogenesis Disorder)
Clinical Image
Source: Wikipedia - Zellweger syndrome - CC BY 4.0
Case Presentation
A newborn presents with severe hypotonia, poor feeding, and seizures within the first hours of life. Physical examination reveals distinctive craniofacial features including a high forehead, flattened facial profile, and large anterior fontanelle. Hepatomegaly is noted on abdominal examination. Laboratory studies show elevated very long-chain fatty acids (VLCFAs) in plasma, elevated phytanic acid, and reduced plasmalogens in red blood cells. Liver biopsy with electron microscopy confirms absence of peroxisomes. Genetic testing reveals mutations in PEX genes involved in peroxisome biogenesis. The diagnosis is Zellweger syndrome, the most severe form of peroxisome biogenesis disorders. Without functional peroxisomes, cells cannot perform beta-oxidation of VLCFAs, synthesize plasmalogens essential for myelin and cell membranes, or perform other critical peroxisomal functions. The prognosis is poor, with most affected infants dying within the first year from respiratory failure or hepatic dysfunction.
Key Learning Points
- Zellweger syndrome demonstrates the essential role of peroxisomes in very long-chain fatty acid metabolism and plasmalogen synthesis
- Elevated plasma VLCFAs are a key diagnostic marker, reflecting the inability to oxidize these fatty acids without functional peroxisomes
- This disorder illustrates how organelle dysfunction leads to multi-system disease, particularly affecting the brain, liver, and kidneys - tissues with high metabolic demands