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

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.

Study Overview

• Status: Recruiting
• 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

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.

• Study Type: Observational
• Enrollment (Estimated): 244

Contacts and Locations

• Study Contact: Name: Nancy E Braverman, MD, MS; Phone Number: 23404 (1) 514-934-1934; Email: nancy.braverman@mcgill.ca
• Study Contact Backup: Name: Evelyn M Zavacky, MSc; Phone Number: 23403 (1) 514-934-1934; Email: pbd.genetics@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Research Institute of the McGill University Health Center
      • Principal Investigator: Nancy E Braverman, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any patient with a PBD diagnosis- or related single enzyme/protein defect

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Documentation of the clinical findings	Clinical findings include but are not limited to: life span, growth parameters, development, vision, hearing, neurological examinations, renal problems, adrenal function, skeletal problems, and any other system involvement.	Yearly up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peroxisome function testing	To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate.	Yearly up to 10 years
Development of leukodystrophy	Identification of patterns and course by MRI	Yearly up to 10 years
Scoring of fundus photography (OCT and FAF)	Identification of patterns and course	Yearly up to 10 years
Genotype-phenotype correlation	Correlation of mutation type to peroxisome biochemistry, number and type of disease complications.	Yearly up to 10 years
Frequency of various disease complications and identification of risk factors in the PBD population	Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones	Yearly up to 10 years
Development of care management guideline resource for adolescents and adults with PBD-ZSD	Medical issues (Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones), main challenges, and the pediatric-to-adult transition experience will be included in PBD-ZSD adult-specific management guidelines	Yearly up to 10 years

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Nancy E Braverman, MD, MS, McGill University Health Center, Montreal Childrens Hopital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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/
• 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/
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: August 10, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimated): August 17, 2012

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: ARD; Peroxisome biogenesis disorders; PBD; Zellweger spectrum disorder; Rhizomelic chondrodysplasia punctata; DBP; ACOX1; AMACR; ACBD5; ZSD; RCDP; ACOX2; ABCD3; Adult Refsum; PHYH; SCPx; RCDP1; RCDP2; RCDP3
• Additional Relevant MeSH Terms: Urogenital Diseases; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Congenital Abnormalities; Abnormalities, Multiple; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Nervous System Malformations; Osteochondrodysplasias; Bone Diseases, Developmental; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Peroxisomal Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Chondrodysplasia Punctata; Zellweger Syndrome; Refsum Disease; Chondrodysplasia Punctata, Rhizomelic; Pseudo-Zellweger syndrome; Alpha-Methylacyl-CoA Racemase Deficiency; Peroxisomal ACYL-COA oxidase deficiency; Peroxisome biogenesis disorders; Rhizomelic chondrodysplasia punctata, type 1
• Other Study ID Numbers: 11-090-PED