OMIM ID:
Peroxisome Biogenesis Disorder 1A (Zellweger)
Alternate Names
Defective Genes
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
Inheritance
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).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.