Activity of phosphomannomutase 2 in patients with suspected congenital disorder of glycosylation
Authors:
H. Hansíková; N. Ondrušková; T. Honzík; K. Veselá; E. Horová; Š. Švecová; M. Tesařová; J. Zeman
Authors‘ workplace:
Klinika dětského a dorostového lékařství, 1. lékařská fakulta Univerzity Karlovy a Všeobecná fakultní nemocnice v Praze
Published in:
Klin. Biochem. Metab., 24, 2016, No. 2, p. 67-74
Overview
Objective:
Aim of study was to establish a method for determining the activity of phosphomannomutase 2 (PMM2) and phosphomannose isomerase (PMI) as a control enzyme in isolated lymphocytes and cultured skin fibroblasts and use it as a differential diagnostic step in a group of 18 patients with suspected CDG syndrome type I.
Design:
Original paper.
Settings:
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague
Material and methods:
Cohort of samples consists of 16 isolated lymphocytes and 8 cultured skin fibroblasts lines from 18 patients from 15 unrelated families with high clinical suspicion for CDG syndrome type I. Group of controls consisted of 59 lymphocytes and 29 fibroblasts cell lines from disease free patients. Activities PMM2 and PMI were measured spectrophotometrically at 37 °C as the reduction of NADP+ to NADPH at 340 nm.
Results:
Statistically significant correlation between activity of PMM2 and PMI and age or gender in lymphocytes or cultured fibroblasts was not found. PMM2 activity in lymphocytes in the control group was from 0.34 to 2.58 nmol/min/mg (2.5% to 97.5% percentile) and in fibroblasts from 0.44 to 9.0 nmol/min/mg. PMM2 activity in lymphocytes in the group of patients was low (0.02-0.18 nmol/min/mg, interquartile range, controls 0.73-1.42 nmol/min/mg, p <0.001). PMM2 activity in fibroblasts from patients was also low (0.2-0.66 nmol/min/mg, controls 1.06-3.17 nmol/min/mg, p<0.001). PMM2 / PMI ratio in patients was significantly decreased in both tissues (p<0.001). The diagnosis of PMM2-CDG was confirmed by finding of mutations in PMM2 gene in all 18 patients.
Conclusion:
Measurement of PMM2 activity in lymphocytes or cultured fibroblasts allows to quickly diagnose PMM2-CDG, the most common congenital disorder of glycosylation
Keywords:
congenital disorders of glycosylation (CDG), phosphomannomutase (PMM2), phosphomannose isomerase (PMI).
Sources
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