TY - JOUR
T1 - Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata
AU - Fallatah, Wedad
AU - Schouten, Monica
AU - Yergeau, Christine
AU - di Pietro, Erminia
AU - Engelen, Marc
AU - Waterham, Hans R.
AU - Poll-The, Bwee Tien
AU - Braverman, Nancy
N1 - Funding Information: This work was supported by E-Rare-3 Joint Translational Call (2015) supported by Canadian Institute of Health Research and Fonds de Recherche du Quebec Sante (NB) and The Netherlands Organization of Health Research and Development (HRW and BTPT), and a scholarship from King AbdulAziz University (WF). We would like to thank all RCDP families and patients for their participation in this manuscript. We give special thanks to RhizoKids International and RCDP Registry at Nemours Alfred I. duPont Hospital for Children for assistance to connect with RCDP families. We thank Dr. Yasmin D'Souza for her assistance in collecting medical records. We also thank Ann Moser for assistance with biochemical evaluations. We would like to acknowledge BioRender.com for support to create Figure 1. Publisher Copyright: © 2020 SSIEM.
PY - 2021/7
Y1 - 2021/7
N2 - Rhizomelic chondrodysplasia punctata (RCDP) is a heterogenous group of disorders due to defects in genes encoding peroxisomal proteins required for plasmalogen (PL) biosynthesis, specifically PEX7 and PEX5 receptors, or GNPAT, AGPS and FAR1 enzymes. Most patients have congenital cataract and skeletal dysplasia. In the classic form, there is profound growth restriction and psychomotor delays, with most patients not advancing past infantile developmental milestones. Disease severity correlates to erythrocyte PL levels, which are almost undetectable in severe (classic) RCDP. In milder (nonclassic) forms, residual PL levels are associated with improved growth and development. However, the clinical course of this milder group remains largely unknown as only a few cases were reported. Using as inclusion criteria the ability to communicate and walk, we identified 16 individuals from five countries, ages 5-37 years, and describe their clinical, biochemical and molecular profiles. The average age at diagnosis was 2.6 years and most had cataract, growth deficiency, joint contractures, and developmental delays. Other major symptoms were learning disability (87%), behavioral issues (56%), seizures (43%), and cardiac defects (31%). All patients had decreased C16:0 PL levels that were higher than in classic RCDP, and up to 43% of average controls. Plasma phytanic acid levels were elevated in most patients. There were several common, and four novel, PEX7, and GNPAT hypomorphic alleles in this cohort. These results can be used to support earlier diagnosis and improve management in patients with mild RCDP.
AB - Rhizomelic chondrodysplasia punctata (RCDP) is a heterogenous group of disorders due to defects in genes encoding peroxisomal proteins required for plasmalogen (PL) biosynthesis, specifically PEX7 and PEX5 receptors, or GNPAT, AGPS and FAR1 enzymes. Most patients have congenital cataract and skeletal dysplasia. In the classic form, there is profound growth restriction and psychomotor delays, with most patients not advancing past infantile developmental milestones. Disease severity correlates to erythrocyte PL levels, which are almost undetectable in severe (classic) RCDP. In milder (nonclassic) forms, residual PL levels are associated with improved growth and development. However, the clinical course of this milder group remains largely unknown as only a few cases were reported. Using as inclusion criteria the ability to communicate and walk, we identified 16 individuals from five countries, ages 5-37 years, and describe their clinical, biochemical and molecular profiles. The average age at diagnosis was 2.6 years and most had cataract, growth deficiency, joint contractures, and developmental delays. Other major symptoms were learning disability (87%), behavioral issues (56%), seizures (43%), and cardiac defects (31%). All patients had decreased C16:0 PL levels that were higher than in classic RCDP, and up to 43% of average controls. Plasma phytanic acid levels were elevated in most patients. There were several common, and four novel, PEX7, and GNPAT hypomorphic alleles in this cohort. These results can be used to support earlier diagnosis and improve management in patients with mild RCDP.
KW - mild (nonclassic) phenotype
KW - peroxisomal disorders
KW - plasmalogen
KW - rhizomelic chondrodysplasia punctata (RCDP)
UR - http://www.scopus.com/inward/record.url?scp=85099740180&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jimd.12349
DO - https://doi.org/10.1002/jimd.12349
M3 - Article
C2 - 33337545
SN - 0141-8955
VL - 44
SP - 1021
EP - 1038
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 4
ER -