title: Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.
abstract: 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.
authors.affiliation: McGill University Health Centre, 1001 Décarie Blvd Block E, EM02230, Montreal, QC H4A3J1, Canada. Electronic address: nancy.braverman@mcgill.ca.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.affiliation: Department of Neurology, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN 55455, USA,. Electronic address: gvraymon@umn.edu.
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, 985456 Nebraska Medical Center - MMI 3062, Omaha, NE 68198-5456, USA. Electronic address: wrizzo@umnc.edu.
authors.forename: William B
authors.initials: WB
authors.lastname: Rizzo
authors.affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, 707 N. Broadway, Baltimore, MD 21205, USA. Electronic address: mosera@kennedykrieger.org.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Moser
authors.affiliation: Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Stephen A. Wynn Institute for Vision Research, 200 Hawkins Drive, Iowa City, IA 52242, USA. Electronic address: mark-wilkinson@uiowa.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wilkinson
authors.affiliation: Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Stephen A. Wynn Institute for Vision Research, 200 Hawkins Drive, Iowa City, IA 52242, USA. Electronic address: edwin-stone@uiowa.edu.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.affiliation: Institute of Genetic Medicine and Department of Neurology, Johns Hopkins University School of Medicine, CMSC1004B, 600 N Wolfe Street, Baltimore, MD 21287, USA. Electronic address: ssteinb8@jhmi.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Steinberg
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Duncan Neurological Research Institute, DNRI-1050, Houston, TX 77030, USA. Electronic address: michael.wangler@bcm.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wangler
authors.affiliation: Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, 985440 Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: erush@unmc.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Rush
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, 1975 Zonal Ave, Los Angeles, CA 90033, USA. Electronic address: hacia@usc.edu.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Hacia
authors.affiliation: Global Foundation for Peroxisomal Disorders, 5147 S. Harvard Avenue, Suite 181, Tulsa, OK 74135, USA. Electronic address: mousumi@thegfpd.org.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Bose
mesh_terms: D000328:Adult; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D018901:Peroxisomal Disorders / Q000175:diagnosis* / Q000628:therapy*; D020675:Peroxisomes / Q000235:genetics; D010641:Phenotype; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D058499:Retinal Dystrophies / Q000209:etiology / Q000503:physiopathology; D015211:Zellweger Syndrome / Q000175:diagnosis* / Q000628:therapy*
chemical_list: D008565:Membrane Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human
keywords: PEX genes; Peroxisome biogenesis disorders; Retinal dystrophy; Sensorineural hearing loss; Treatment guidelines; Very long-chain fatty acids; Zellweger spectrum disorder