Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

NCT ID: NCT01668186

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 244 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2031-01-31

Brief Summary

The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of phenotypes poorly characterized and the natural history not yet systematically reported. Our aims are to further define this population clinically, biochemically and genetically. The investigators will prospectively follow patients from Canada, the US and internationally, and collect data from medical evaluations, blood, urine and imaging studies that would be performed on a clinical care basis. For patients who are unable to attend our clinic, we will collect all medical records and images since birth as well as subsequent records/images for the next 5 years or until the end of the study. Clinical data from medical records will be banked in our Peroxisomal Disorder Research Databank and Biobank. The investigators will use this information to identify standards of care and improve management.

Detailed Description

Participants have the option to be seen in consultation at the McGill University Health Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics, Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images will be collected, retrospectively and prospectively, until the end of the study, and entered anonymously in a database. Biospecimens will be collected to identify new biomarkers. Candidate drugs will be evaluated for recovery of peroxisome functions in cultured fibroblasts.

Conditions

Peroxisome Biogenesis Disorder; Zellweger Spectrum Disorder; RCDP - Rhizomelic Chondrodysplasia Punctata; D-Bifunctional Protein Deficiency; Alpha-Methylacyl-CoA Racemase Deficiency; Peroxisomal Acyl-CoA Oxidase Deficiency; Peroxisomal Acyl-CoA Oxidase 2 Deficiency; ATP Binding Cassette Subfamily D Member 3 Gene Mutation; ACBD5 (AcylCoA Binding Domain 5) Deficiency; Adult Refsum Disease; Sterol Carrier Protein 2 Deficiency

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Patients diagnosed with a peroxisomal disorder

Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Diagnosis of PBD or
• Single peroxisome enzyme/protein defect with phenotype similar to PBD

Exclusion Criteria

• Not a PBD
• Not a single peroxisome enzyme/protein defect with phenotype similar to PBD

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Nancy Braverman

MD, M.Sc. Professor, Depts. of Human Genetics and Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy E Braverman, MD, MS

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Center, Montreal Childrens Hopital

Locations

Research Institute of the McGill University Health Center

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Nancy E Braverman, MD, MS

Role: CONTACT

nancy.braverman@mcgill.ca

(1) 514-934-1934 ext. 23404

Evelyn M Zavacky, MSc

Role: CONTACT

pbd.genetics@mcgill.ca

(1) 514-934-1934 ext. 23403

References

Yergeau C, Coussa RG, Antaki F, Argyriou C, Koenekoop RK, Braverman NE. Zellweger Spectrum Disorder: Ophthalmic Findings from a New Natural History Study Cohort and Scoping Literature Review. Ophthalmology. 2023 Dec;130(12):1313-1326. doi: 10.1016/j.ophtha.2023.07.026. Epub 2023 Aug 2.

Reference Type: DERIVED

PMID: 37541626 (View on PubMed)

Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/

Reference Type: BACKGROUND

PMID: 20301621 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26750748 (View on PubMed)

Braverman NE, Carroll R, Muss C, Fallatah W, Jain M. PEX7-Related Rhizomelic Chondrodysplasia Punctata. 2001 Nov 16 [updated 2025 Aug 7]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/

Reference Type: BACKGROUND

PMID: 20301447 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26643206 (View on PubMed)

Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283. doi: 10.1038/gim.2017.262. Epub 2018 Feb 8.

Reference Type: BACKGROUND

PMID: 29419819 (View on PubMed)

Cheung A, Argyriou C, Yergeau C, D'Souza Y, Riou E, Levesque S, Raymond G, Daba M, Rtskhiladze I, Tkemaladze T, Adang L, La Piana R, Bernard G, Braverman N. Clinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series. Neurogenetics. 2022 Apr;23(2):115-127. doi: 10.1007/s10048-022-00684-7. Epub 2022 Feb 2.

Reference Type: DERIVED

PMID: 35106698 (View on PubMed)

Lee J, Yergeau C, Kawai K, Braverman N, Geleoc 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.

Reference Type: DERIVED

PMID: 34534157 (View on PubMed)

Other Identifiers

11-090-PED

Identifier Type: -

Identifier Source: org_study_id