Wegwerth Peter J, White Amy L, Stoway Stephanie D, Loken Perry R, Oglesbee Devin, Matern Dietrich, Tortorelli Silvia, Raymond Kimiyo M, Braverman Nancy E, Gavrilov Dimitar K
Division of Laboratory Genetics and Genomics, Mayo Clinic, Rochester, Minnesota, USA.
Department of Information Technology, Mayo Clinic, Rochester, Minnesota, USA.
J Inherit Metab Dis. 2023 Nov;46(6):1159-1169. doi: 10.1002/jimd.12682. Epub 2023 Oct 31.
Measurement of plasmalogens is useful for the biochemical diagnosis of rhizomelic chondrodysplasia punctata (RCDP) and is also informative for Zellweger spectrum disorders (ZSD). We have developed a test method for the simultaneous quantitation of C16:0, C18:0, and C018:1 plasmalogen (PG) species and their corresponding fatty acids (FAs) in dried blood spots (DBS) and erythrocytes (RBC) by using capillary gas chromatography-mass spectrometry. Normal reference ranges for measured markers and 10 calculated ratios were established by the analysis of 720 and 473 unaffected DBS and RBC samples, respectively. Determination of preliminary disease ranges was made by using 45 samples from 43 unique patients: RCDP type 1 (DBS: 1 mild, 17 severe; RBC: 1 mild, 6 severe), RCDP type 2 (DBS: 2 mild, 1 severe; RBC: 2 severe), RCDP type 3 (DBS: 1 severe), RCDP type 4 (RBC: 2 severe), and ZSD (DBS: 3 severe; RBC: 2 mild, 7 severe). Postanalytical interpretive tools in Collaborative Laboratory Integrated Reports (CLIR) were used to generate an integrated score and a likelihood of disease. In conjunction with a review of clinical phenotype, phytanic acid, and very long-chain FA test results, the CLIR analysis allowed for differentiation between RCDP and ZSD. Data will continue to be gathered to improve CLIR analysis as more samples from affected patients with variable disease severity are analyzed. The addition of DBS analysis of PGs may allow for at-home specimen collection and second-tier testing for newborn screening programs.
缩醛磷脂的测量对于诊断肢根型点状软骨发育不良（RCDP）的生化诊断很有用，对泽尔韦格谱系障碍（ZSD）也具有参考价值。我们开发了一种检测方法，通过毛细管气相色谱 - 质谱法同时定量干血斑（DBS）和红细胞（RBC）中C16:0、C18:0和C018:1缩醛磷脂（PG）种类及其相应的脂肪酸（FAs）。通过分别分析720份未受影响的DBS样本和473份未受影响的RBC样本，建立了测量标志物和10个计算比率的正常参考范围。使用来自43例独特患者的45份样本确定初步疾病范围：1型RCDP（DBS：1例轻度，17例重度；RBC：1例轻度，6例重度），2型RCDP（DBS：2例轻度，1例重度；RBC：2例重度），3型RCDP（DBS：1例重度），4型RCDP（RBC：2例重度），以及ZSD（DBS：3例重度；RBC：2例轻度，7例重度）。协作实验室综合报告（CLIR）中的分析后解释工具用于生成综合评分和疾病可能性。结合临床表型、植烷酸和极长链脂肪酸检测结果，CLIR分析有助于区分RCDP和ZSD。随着对更多疾病严重程度不同的受影响患者样本进行分析，将继续收集数据以改进CLIR分析。PGs的DBS分析补充可能允许在家中采集样本，并用于新生儿筛查项目的二级检测。
