Handbook of Genetic Counseling/Zellweger Syndrome
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Genetic Etiology 
- Mode of inheritance: Autosomal recessive with non-allelic heterogeneity.
- Chromosome location: 2p15, 1q22, 12p13.3, 7q21-q22, 6q23-q24
- Molecular genetics: Phenotype caused by mutation in any of several genes involved: in peroxisome biogenesis (peroxi-1, -2, -3, -5, -6, or -12).
- Peroxisomes are subcellular organelles that play a role in lipid metabolism--these are absent
Incidence and Carrier Frequency 
- Incidence is 1 in 40,000. Males and females are affected equally.
Clinical Features 
- Craniofacial Features
- Flat occiput and face
- Anteverted nares
- Epicanthal folds
- Brushfield spots
- High forehead
- Large fontanels
- Shallow orbits
- Ocular Features
- Hypoplastic optic disk
- Auditory Features
- Abnormal helices
- Neurological Features
- Early developmental delay
- Brain migrational abnormalities
- MR in survivors
- Brain malformations including microgyria, heteropias, subependymal cysts, astrocytosis and gliosis, hypoplastic corpus callosum, hypoplastic olfactory lobes
- Single palmar creases
- Joint contractures
- Stippled epiphyses
- Cardiovascular Features
- Cardiac septal defects
- Other Features
- Postnatal growth deficiency and low birth weight
- Poor suck
- Albuminuria and cysts of glomeruli in kidneys
- Elevated serum iron level and evidence of excess iron storage
- Absent liver peroxisomes
Age of Onset, Natural History, Life Span 
- Most babies are born breech and exhibit failure to thrive. Some developed icterus and bloody stool.
- Vast majority of children die within the first year of life. Those who survive have profound mental retardation. Average life span is 12-13 weeks.
- Diagnosis is made through DNA testing.
- Increase in plasma and fibroblasts of very-long-chain fatty acids and lack of dihydroxyacetone phosphate acyltransferase (DHAP-AT) are biochemical markers for this syndrome
Surveillance, Management, and Treatment Options 
- Multidisciplinary early intervention
- Oral administration of plasmalogens
- Restricted phytanic acid intake
- OT, PT, hearing aids, nutrition
- Skeletal surveys (X-rays, CT and MRI)
- Renal and abdominal ultrasounds
Differential Diagnoses 
- Down syndrome is the most common
The information in this outline was last updated in 2002.