Transferrin D protein variants in the diagnosis of congenital disorders of glycosylation (CDG)

Abstract

Congenital disorders of glycosylation are a rapidly growing group of inherited (neuro)metabolic disorders characterized by defects in glycosylation of proteins and lipids. This study discusses an analytical problem in the differentiation between hypoglycosylation and transferrin (Tf) protein variants. Analysis of serum Tf by isoelectric focusing is used as a common method suitable for screening 19 out of a total of 22 types of glycosylation defects identified so far. In three members of a family, several indicators showed evidence of a Tf protein variant, however, routine neuraminidase-based demonstration failed to confirm this result. On the assumption that we should be able to exclude Tf protein variants at the screening-level of the diagnostic algorithm, our concern is a possible cause of our failure to confirm some of the Tf D variants (in contrast to the other C, B and D allelic combinations that are commonly well identified). Several explanations are discussed.

Improved tryptic digestion assisted with an acid-labile anionic surfactant for the separation and characterization of glycopeptide glycoforms of a proteolytic-resistant glycoprotein by capillary electrophoresis time-of-flight mass spectrometry

“…The development of a CE‐MS method able to separate and detect the glycopeptide glycoforms of Tf could solve the most impending problems of routine methods for the analysis of Tf in serum samples. These routine methods usually consist in the analysis of intact Tf by IEF or anion exchange LC with UV detection . However, IEF is an arduous and time‐consuming technique which is not suitable for automation and UV detection does not allow the reliable characterization of Tf glycoforms.…”

Вродени Дефекти На Гликозилиране

“…По-чувствителни процедури, базирани на директна детекция на нарушената конверсия на субстрат/продукт (манозо-1-фосфат до манозо-6фосфат при PMM2-CDG) с AEC-PAD. Посредством този метод се установява значително намалена активност в облигатни хетерозиготи [43].…”

Metabolic stroke in childhood: Diagnostic approach and suggestions for therapy

“…CDG can cause generalized coagulopathy and hemorrhagic stroke [22]; however, ischemic stroke with focal cerebral necrosis has been described, although the pathomechanism is not yet understood well [23,24]. The diagnosis of CDG can be supported by laboratory studies for transferrin isoelectric focusing and genetic analysis, but it is complicated by significant genetic heterogeneity [25,26].…”