Peroxisome Biogenesis Disorder 1A (Zellweger)

Background and History: 

This syndrome is named after Hans Ulrich Zellweger, a Swiss-American pediatrician who first described it.  The condition is sometimes called a leukodystrophy because of the brain characteristics found in infants with this syndrome.  Newer terminology refers to this disorder as Perioxismal Biogenesis Disorder - Zellweger Spectrum Disorder.

Clinical Correlations: 

This is a severe disease resulting from metabolic defects that causes a variety of signs and symptoms.  Infants are usually floppy at birth and may have feeding problems.  The liver and sometimes the spleen are enlarged and jaundice is often present.  They have severe motor and mental retardation although for those infants who survive beyond 6 months there can be some improvement.  Seizures are not uncommon.  Hearing loss and vision problems are part of the clinical picture.  The face and skull are unusual with a prominent forehead and wide set eyes.  Cataracts are common and the retina and optic nerves are usually abnormal.  ‘Dancing eyes’ (nystagmus) is often seen.

Genetics: 

This disorder results from mutations in a large number of genes that impact liver and brain metabolism.  Inheritance follows an autosomal recessive (horizontal) pattern in which both normal parents give their single mutant gene to their children who therefore present with this disease only if they have two mutations.

Diagnosis and Prognosis: 

The prognosis is not good.  Few infants survive beyond 6 months but numerous exceptions have been reported.  The diagnosis is based on the clinical and biochemical features.  No effective treatment is available.

Additional Information