Zellweger Syndrome
Introduction
Zellweger syndrome (ZS) is the most severe form of the Zellweger spectrum disorders (ZSDs), a group of inherited peroxisome biogenesis disorders. It is characterized by the reduction or absence of functional peroxisomes in cells throughout the body.
Key Points
- Also known as: Cerebrohepatorenal syndrome
- Inheritance: Autosomal recessive
- Age of onset: Congenital
- Prevalence: 1:50,000 to 1:100,000 births
- Life expectancy: Usually less than 1 year
Clinical Features
Craniofacial Features
- High forehead with prominent sutures
- Large anterior fontanel
- Characteristic facies with high forehead
- Epicanthal folds
- Broad nasal bridge
- Micrognathia
Neurological Manifestations
- Profound hypotonia from birth
- Poor feeding and sucking
- Seizures (often present from birth)
- Nystagmus
- Impaired hearing and vision
- Absence of reflexes
Organ System Involvement
- Hepatomegaly with liver dysfunction
- Renal cysts
- Skeletal abnormalities
- Cardiac defects (common)
- Cataracts
Diagnosis
Laboratory Findings
- Elevated very long chain fatty acids (VLCFAs)
- Elevated plasma pipecolic acid
- Elevated plasma phytanic and pristanic acids
- Abnormal plasmalogens in erythrocytes
Imaging Studies
- Brain MRI showing:
- Neuronal migration defects
- Demyelination
- Germinolytic cysts
- Renal ultrasound showing cortical cysts
- Skeletal survey for calcific stippling
Confirmatory Testing
- Genetic testing for PEX genes
- Fibroblast complementation studies
- Biochemical markers in cultured fibroblasts
Management
Supportive Care
- Feeding support and nutrition management
- Seizure control
- Physical therapy
- Respiratory support
- Management of liver dysfunction
Monitoring
- Regular growth assessment
- Developmental evaluation
- Liver function tests
- Hearing and vision assessment
- Cardiac monitoring
Medical Interventions
- Anti-epileptic medications as needed
- Vitamin K supplementation
- Management of coagulopathy
- Treatment of infections
Genetics & Inheritance
Genetic Basis
- Mutations in PEX genes (most commonly PEX1, PEX6, PEX10, PEX12)
- Affects peroxisome assembly and function
- Over 14 PEX genes identified
Inheritance Pattern
- Autosomal recessive inheritance
- 25% recurrence risk in future pregnancies
- Carrier testing available for family members
Prognosis & Counseling
Natural History
- Progressive deterioration
- Most infants do not survive beyond first year
- Death usually due to respiratory complications or liver failure
Family Support
- Genetic counseling for families
- Psychological support
- Connection with support groups
- Palliative care discussion
