Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata.
J Inherit Metab Dis
; 44(4): 1021-1038, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-33337545
ABSTRACT
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 C160 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Condrodisplasia Punctata Rizomélica
/
Estudios de Asociación Genética
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Gráficos de Crecimiento
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Inherit Metab Dis
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá