Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Mol Genet Metab. 2016 Mar;117(3):313-21. doi: 10.1016/j.ymgme.2015.12.009. Epub 2015 Dec 23.


Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.

Keywords: PEX genes; Peroxisome biogenesis disorders; Retinal dystrophy; Sensorineural hearing loss; Treatment guidelines; Very long-chain fatty acids; Zellweger spectrum disorder.

Publication types

  • Review

MeSH terms

  • Adult
  • Genetic Testing
  • Hearing Loss, Sensorineural / etiology
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • Membrane Proteins / genetics
  • Mutation*
  • PHEX Phosphate Regulating Neutral Endopeptidase / genetics
  • Peroxisomal Disorders / diagnosis*
  • Peroxisomal Disorders / therapy*
  • Peroxisomes / genetics
  • Phenotype
  • Practice Guidelines as Topic
  • Precision Medicine
  • Retinal Dystrophies / etiology
  • Retinal Dystrophies / physiopathology
  • Zellweger Syndrome / diagnosis*
  • Zellweger Syndrome / therapy*


  • Membrane Proteins
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human

Supplementary concepts

  • Peroxisome biogenesis disorders