Peroxisome Biogenesis Disorder 1A (Zellweger)

Clinical Characteristics
Ocular Features: 

Ocular signs resemble those of other peroxisomal disorders with cataracts and retinopathy.  The lethal consequences of ZWS have hampered delineation of the full spectrum of ocular manifestations but many infants have these features plus optic atrophy and horizontal nystagmus.  Most infants do not follow light.  Pupillary responses may be normal in early stages but disappear later. Hypertelorism has been described but metrics are often normal.

Systemic Features: 

Many infants have hepatomegaly at birth and may develop splenomegaly as well.  Jaundice often occurs with intrahepatic biliary dysgenesis.   Severe hypotonia is present at birth but improves in those patients who survive for several years.  Psychomotor retardation can be profound and seizures may occur but sensory examinations are normal.  Most infants have a peculiar craniofacial dysmorphology with frontal bossing, large fontanels, and wide set eyes.  Pipecolic acid levels are low in serum and absent in the CSF.  Most infants do not survive beyond 6 months of age.

 

Genetics

This is a peroxisome biogenesis disorder with a complex biochemical profile resulting from a large number of mutations in at least 13 PEX genes.  It is inherited in an autosomal recessive pattern.

What was formerly called Zellweger Syndrome is now more properly called Zellweger Spectrum Disorder, or sometimes a peroxisomal biogenesis disorder in the Zellweger spectrum of disorders.  The spectrum also includes neonatal adrenoleukodystrophy (601539) and Infantile Refsum disease (601539). 

Treatment
Treatment Options: 

No effective treatment is available.

References
Article Title: 

References

Wanders RJ, Klouwer FC, Ferdinandusse S, Waterham HR, Poll-The BT. Clinical and Laboratory Diagnosis of Peroxisomal Disorders. Methods Mol Biol. 2017;1595:329-342.

PubMedID: 28409475

Ebberink MS, Kofster J, Wanders RJ, Waterham HR. Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. Hum Mutat. 2010 Jan;31(1):E1058-70.

PubMedID: 19877282

Krause C, Rosewich H, G?SSrtner J. Rational diagnostic strategy for Zellweger syndrome spectrum patients. Eur J Hum Genet. 2009 Jun;17(6):741-8.

PubMedID: 19142205

Govaerts L, Monnens L, Tegelaers W, Trijbels F, van Raay-Selten A. Cerebro-hepato-renal syndrome of Zellweger: clinical symptoms and relevant laboratory findings in 16 patients. Eur J Pediatr. 1982 Oct;139(2):125-8.

PubMedID: 7151832