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

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ClinicalTrials.gov Identifier: NCT01668186

Recruitment Status : Recruiting

First Posted : August 17, 2012

Last Update Posted : April 12, 2022

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Sponsor:

Information provided by (Responsible Party):

Nancy Braverman, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study Description

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.

Condition or disease
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

Condition or disease

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 Design

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Study Type :	Observational
Estimated Enrollment :	230 participants
Observational Model:	Cohort
Time Perspective:	Other
Official Title:	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Actual Study Start Date :	January 2012
Estimated Primary Completion Date :	January 2025
Estimated Study Completion Date :	January 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Refsum disease Zellweger spectrum disorder X-linked chondrodysplasia punctata 1 Peroxisomal acyl-CoA oxidase deficiency Alpha-methylacyl-CoA racemase deficiency D-bifunctional protein deficiency

Genetic and Rare Diseases Information Center resources: Rhizomelic Chondrodysplasia Punctata Chondrodysplasia Punctata Syndrome Peroxisome Biogenesis disorder-Zellweger Syndrome Spectrum Refsum Disease D-bifunctional Protein Deficiency Pseudoneonatal Adrenoleukodystrophy Leukoencephalopathy - Dystonia - Motor Neuropathy Zellweger Syndrome Peroxisomal Biogenesis Disorders Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Roussy Levy Syndrome Mucopolysaccharidosis Type IV

U.S. FDA Resources

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

Documentation of the clinical findings [ Time Frame: Yearly up to 10 years ]
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.

Secondary Outcome Measures :

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

Biospecimen Retention: Samples With DNA

blood, dried blood spots, urine, and specimens obtained for other e.g. cultured fibroblasts, liver biopsies

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

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

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01668186

Contacts

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Contact: Nancy E Braverman, MD, MS	(1) 514-934-1934 ext 23404	nancy.braverman@mcgill.ca
Contact: Christine Yergeau, MSc	(1) 514-934-1934 ext 23403	pbd.genetics@mcgill.ca

Locations

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

Sponsors and Collaborators

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

Investigators

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Principal Investigator:	Nancy E Braverman, MD, MS	McGill University Health Center, Montreal Childrens Hopital

More Information

Publications:

Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/

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. Review.

Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober M. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cheung A, Argyriou C, Yergeau C, D'Souza Y, Riou É, Lévesque 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, 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.

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Responsible Party:	Nancy Braverman, MD, M.Sc. Professor, Depts. of Human Genetics and Pediatrics, McGill University Health Centre/Research Institute of the McGill University Health Centre
ClinicalTrials.gov Identifier:	NCT01668186
Other Study ID Numbers:	11-090-PED
First Posted:	August 17, 2012 Key Record Dates
Last Update Posted:	April 12, 2022
Last Verified:	April 2022

Keywords provided by Nancy Braverman, McGill University Health Centre/Research Institute of the McGill University Health Centre:


Peroxisome biogenesis disorders PBD Zellweger spectrum disorder Rhizomelic chondrodysplasia punctata DBP ACOX1 AMACR ARD ACBD5 ZSD	RCDP ACOX2 ABCD3 Adult Refsum PHYH SCPx RCDP1 RCDP2 RCDP3

Additional relevant MeSH terms:

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Chondrodysplasia Punctata, Rhizomelic Chondrodysplasia Punctata Zellweger Syndrome Refsum Disease Peroxisomal Disorders Protein Deficiency Disease Pathologic Processes Deficiency Diseases Malnutrition Nutrition Disorders Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Brain Diseases, Metabolic, Inborn	Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Hereditary Sensory and Motor Neuropathy Nervous System Malformations Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Polyneuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Congenital Abnormalities Liver Diseases Digestive System Diseases Kidney Diseases

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