Clinical trial NCT01668186: Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Official title: Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Study type: OBSERVATIONAL
Overall 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
Keywords: 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
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2012-08-17
Enrollment: 244
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any patient with a PBD diagnosis- or related single enzyme/protein defect

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.

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

Primary outcomes:
measure: Documentation of the clinical findings
timeFrame: Yearly up to 10 years
Secondary outcomes:
measure: Peroxisome function testing
timeFrame: Yearly up to 10 years
measure: Development of leukodystrophy
timeFrame: Yearly up to 10 years
measure: Scoring of fundus photography (OCT and FAF)
timeFrame: Yearly up to 10 years
measure: Genotype-phenotype correlation
timeFrame: Yearly up to 10 years
measure: Frequency of various disease complications and identification of risk factors in the PBD population
timeFrame: Yearly up to 10 years
measure: Development of care management guideline resource for adolescents and adults with PBD-ZSD
timeFrame: Yearly up to 10 years
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Center
state: Quebec
Study officials:
affiliation: McGill University Health Center, Montreal Childrens Hopital
name: Nancy E Braverman, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Feldman J, 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/
citation: 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.
citation: Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober MB. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Feldman J, 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/
citation: 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.
citation: 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.
citation: 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.
citation: 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.