Natural History Study

On this page:

I. Information for students and researchers

a. Research projects in the Natural History Study

b. Previous publications

II. Information for participants and their families

a. Steps to participate in the Natural History Study

For students and researchers

Peroxisomal biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are very rare diseases, with a birth incidence rate of 1 in 50,000 – 1 in 100,000 in the United States. Since it is such a rare disease, our longitudinal natural history study (NHS) on Peroxisome Biogenesis Disorders (NCT01668186) aims to address current gaps in knowledge about ZSD, particularly in its clinical progression and its potential treatments.

By collecting and assessing all of a patient’s medical history through their medical records, the aim of this study is to help doctors provide better care to individuals with peroxisome disorders and to help researchers judge whether future therapies will work by having establishing clinical endpoints. These endpoints need to be well-defined and easily measurable in order for a treatment to be proven to be beneficial. By organizing patient data across hundreds of patients, we can better identify accurate clinical endpoints and build an essential dataset for future clinical trials.

Importantly, this study goes beyond a registry as it is patient-centered. As a part of enrollment, Dr. Braverman and the research coordinator meet each patient and their family in an online meeting. This is important to hear the story from a patient/caretaker perspective. This can help us identify gaps in the medical care system. This call is also useful to answer any questions the family may have. It is also important that the information gained in the study is shared back to the families that have contributed to the study in the first place.

Ongoing projects within the Natural History Study

REDCap database: Since Summer 2025, our team has been working on designing a REDCap database to allow our data to be shared with others. This also involves moving all our data which was previously stored on Microsoft Access.
Development of Patient-Specific Growth Curves in ZSD
Genetic and Clinical Classification of D-Bifunctional Protein Deficiency
Management guidelines for severe ZSD and mild ZSD patients

Projects to be picked up in the Natural History Study

Description of dental abnormalities due to amylogenesis imperfecta in ZSD
Genetic and Clinical Classification of ZSD groups and other related peroxisomal disorders
Review of neurological symptoms and brain MRIs

If you are interested in contributing to any of these projects, please contact the clinical research coordinator with your specific interest and CV at pbd.genetics[at]mcgill.ca.

Previous publications

Cheung ACT , Di Pietro E , Argyriou C , Bareke E , D'Souza Y , Puri RD , Muhammed Shabeer P , Ganetzky R , Goldstein A , Vanderver A , Mohan S , Majewski J , Yergeau C , Braverman N. (2025). Using multiple modalities to confirm diagnosis in patients with suspected peroxisome biogenesis disorders.Molecular genetics and metabolism. 145(1): 109080.

Cheung PEX16

Yergeau C , Coussa RG , Antaki F , Argyriou C, Koenekoop RK , Braverman NE. (2023). Zellweger Spectrum Disorder: Ophthalmic Findings from a New Natural History Study Cohort and Scoping Literature Review.Ophthalmology. 130(12): 1313-1326. Published Refereed?:

Lee J, Yergeau C, Kawai K, Braverman N, Géléoc GSG. A Retrospective Study of Hearing Loss in Patients Diagnosed with Peroxisome Biogenesis Disorders in the Zellweger Spectrum. Ear Hear. 2022 Mar/Apr;43(2):582-591. doi: 10.1097/AUD.0000000000001126. PMID: 34534157; PMCID: PMC8881323.

Anthony Cheung, Catherine Argyriou, Christine Yergeau, Yasmin D’Souza, Emilie Rio, Sebastien Levesque, Gerald Raymond, Mebratu Daba, Irakli Rtskhiladze, Tinatin Tkemaladze, Laura Adang, Roberta La Piana, Genevieve Bernard, Nancy Braverman. (2022). Clinical, neuroradiological, and molecular characterization of patients with mild PEX16 defects: a case series. Neurogenetics. 2(23): 115-127. Last Author Published

Bose M , Yergeau C , D'Souza Y , Cuthbertson DD , Lopez MJ , Smolen AK , Braverman NE. (2022). Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, MetaAnalysis and Medical Chart Review.Cells. 11(12): 1891. Published

Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. 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. PMID: 26750748; PMCID: PMC5214431.

Argyriou C, D'Agostino MD, Braverman N. Peroxisome biogenesis disorders. Transl Sci Rare Dis. 2016 Nov 7;1(2):111-144. doi: 10.3233/TRD-160003. PMID: 29152457; PMCID: PMC5678237.

Rush ET, Goodwin JL, Braverman NE, Rizzo WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab. 2016 Jan;117(1):33-7. doi: 10.1016/j.ymgme.2015.11.009. Epub 2015 Nov 24. PMID: 26643206.

Information for prospective participants and families

Started in 2012, our natural history study (NHS) collects medical records from individuals with peroxisome biogenesis disorders around the world. As a part of this study, Dr. Braverman and the clinical research coordinator will also arrange an online meeting with each family to hear the story from your perspective, answer any questions, and share any insights based on information we have collected from the study. We will also arrange for a translator if your family does not speak English or French.

This study aims to help doctors provide better care to patients with peroxisomal disorders, develop therapies that are most important to patients and help researchers judge whether potential therapies will work when they do arise. It is also important that this information is shared back to the families that have contributed to the study in the first place.

Currently, there are over 300 individuals enrolled in our natural history study across 30 countries worldwide. There have been several research publications based on the information gained in the Natural History Study, including papers on vision, hearing and bone density, amongst others. Projects and publications are always ongoing. We thank every family and individual that takes the time to enroll in the study.

What is it like to enroll in our study?

Contact our clinical coordinator at pbd.genetics[at]mcgill.ca with your interest in our study
Sign a consent form (and if applicable, a “list of hospitals” form that details every institution you or your child has been seen in)
Send or sign for medical records. It may take some time (up to several weeks) for the medical records to be collected by the clinical research coordinator.
After a review of medical records, the clinical coordinator will reach out to plan a meeting with either yourself or you and your child. This will let us see the patient and answer any questions you or your child might have.
After our call, a letter summary will be sent with everything that was discussed in the call, including a review on ZSD and information we have gathered across the natural history study. We also invite you to send us any questions or concerns that come up in the future as you or your child is now enrolled in our study.

If you would like to enroll yourself or a child in our study, or if you have any questions about the process, please email pbd.genetics[at]mcgill.ca.

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