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.

中文翻译：

---

轻度（非经典）根状茎点状软骨发育不良的临床、生化和分子特征

点状根状软骨发育不良 (RCDP) 是一组异质性疾病，原因是编码缩醛磷脂 (PL) 生物合成所需的过氧化物酶体蛋白的基因存在缺陷，特别是 PEX7 和 PEX5 受体，或 GNPAT、AGPS 和 FAR1 酶。大多数患者患有先天性白内障和骨骼发育不良。在经典形式中，存在严重的生长受限和精神运动延迟，大多数患者没有超过婴儿发育里程碑。疾病严重程度与红细胞 PL 水平相关，这在严重（经典）RCDP 中几乎无法检测到。在较温和（非经典）形式中，残留的 PL 水平与改善的生长和发育有关。然而，由于仅报告了少数病例，这一较轻组的临床过程在很大程度上仍然未知。使用沟通和行走的能力作为纳入标准，我们确定了来自五个国家的 16 名年龄在 5-37 岁之间的个体，并描述了他们的临床、生化和分子特征。诊断时的平均年龄为 2.6 岁，大多数患有白内障、生长缺陷、关节挛缩和发育迟缓。其他主要症状是学习障碍 (87%)、行为问题 (56%)、癫痫发作 (43%) 和心脏缺陷 (31%)。所有患者的 C16:0 PL 水平均降低，高于经典 RCDP，平均水平高达 43%。大多数患者的血浆植烷酸水平升高。有几种常见的，四种新颖的，和发育迟缓。其他主要症状是学习障碍 (87%)、行为问题 (56%)、癫痫发作 (43%) 和心脏缺陷 (31%)。所有患者的 C16:0 PL 水平均降低，高于经典 RCDP，平均水平高达 43%。大多数患者的血浆植烷酸水平升高。有几种常见的，四种新颖的，和发育迟缓。其他主要症状是学习障碍 (87%)、行为问题 (56%)、癫痫发作 (43%) 和心脏缺陷 (31%)。所有患者的 C16:0 PL 水平均降低，高于经典 RCDP，平均水平高达 43%。大多数患者的血浆植烷酸水平升高。有几种常见的，四种新颖的，该队列中的PEX7和GNPAT同态等位基因。这些结果可用于支持早期诊断和改善轻度 RCDP 患者的管理。