Dave Mihika B, Dherai Alpa J, Udani Vrajesh P, Ashavaid Tester F
Department of Biochemistry, P. D. Hinduja Hospital & MRC, Veer Savarkar Marg, Mahim, Mumbai, 400016 India.
Department of Pediatric Neurology, P. D. Hinduja Hospital & MRC, Veer Savarkar Marg, Mahim, Mumbai, 400016 India.
Indian J Clin Biochem. 2022 Apr;37(2):238-241. doi: 10.1007/s12291-020-00930-5. Epub 2020 Nov 17.
Advances in molecular sequencing technology has increased the diagnostic yield for Congenital disorder of glycosylation (CDG). However, novel variants or those of uncertain significance (vus) often pose a challenge and in such cases confirmed diagnosis can be warranted through enzyme analysis of these defects. We thus, aimed to optimize leukocyte-based enzyme assays for first two enzymes involved in N-glycosylation pathway i.e. Phosphomannomutase (PMM) and Phosphomannose isomerase (MPI). Study population comprised of 50 healthy non-alcoholic adults and 20 pediatric controls. Leukocyte enzyme activity was measured by monitoring the conversion of NADP to NADPH at 340 nm. The conditions were optimized and precision was assessed for both low and normal activity leukocyte controls. Enzyme activities for PMM and MPI in healthy individuals were measured in the range 1.6-3.9 and 7-20 nmol/min/mg protein respectively and did not vary with age and gender. The precision for both PMM and MPI showed %CV of 19.9 and 19.8 respectively. The enzyme activity in leukocyte pellet was found to be stable for up to 9 months when stored at -80 °C. The enzyme assays are optimized for PMM and MPI and can be used for evaluation of CDG patients in India.
分子测序技术的进步提高了糖基化先天性疾病(CDG)的诊断率。然而,新的变异或意义未明的变异(vus)常常带来挑战,在这种情况下,通过对这些缺陷进行酶分析来确诊是必要的。因此,我们旨在优化基于白细胞的酶分析方法,用于检测参与N-糖基化途径的前两种酶,即磷酸甘露糖变位酶(PMM)和磷酸甘露糖异构酶(MPI)。研究人群包括50名健康的非酒精性成年人和20名儿科对照。通过监测340nm处NADP向NADPH的转化来测量白细胞酶活性。对条件进行了优化,并评估了低活性和正常活性白细胞对照的精密度。健康个体中PMM和MPI的酶活性分别在1.6 - 3.9和7 - 20nmol/min/mg蛋白质范围内测定,且不随年龄和性别而变化。PMM和MPI的精密度分别显示变异系数(%CV)为19.9和19.8。当储存在-80°C时,白细胞沉淀中的酶活性在长达9个月内保持稳定。已对PMM和MPI的酶分析方法进行了优化,可用于评估印度的CDG患者。