Zellweger Spectrum Disorder (ZSD) shows a range of phenotypes depending on the severity of the genetic defect. The most severe forms present during the neonatal or infantile periods and are associated with early death.
Pathogenesis: generalized loss of peroxisome function
Inheritance: usually autosomal recessive
Clinical features:
(1) severe hypotonia
(2) epileptic seizures
(3) failure to thrive
(4) poor feeding
(5) hepatomegaly with hepatic dysfunction and/or cholestasis
(6) craniofacial dysmorphism (flat face, broad nasal bridge, large anterior fontanelle, widely split sutures)
(7) coagulopathy
(8) abnormalities of dental enamel
(9) sensorineural hearing deficit
(10) brain malformation (gyral malformations)
(11) renal cysts
(12) bony stippling (chondrodysplasia punctata) in patella and long bones
Death usually occurs during infancy due to respiratory compromise (progressive apnea, recurrent pneumonia).
