A new strategy implementing mass spectrometry in the diagnosis of congenital disorders of N-glycosylation (CDG)

Objectives: Congenital disorders of N-glycosylation (CDG) are a large group of rare metabolic disorders caused by defects in the most common post-translational modification of proteins. CDGs are often difficult to diagnose as they are manifested with non-specific symptoms and signs. Analysis of serum transferrin (TRF) isoforms, as the classical procedure used to identify a CDG patient, enables to predict pathological steps in the N-linked glycosylation process. Methods: We devised a new strategy based on liquid chromatography-mass spectrometry (LC-MS) for the analysis of TRF isoforms by combining a simple and fast sample preparation with a specific chromatographic cleanup/separation step followed by mass-spectrometric measurement. Single TRF isoform masses were obtained through reconstruction of multiply charged electrospray data collected by quadrupole-MS technology. Hereby, we report the first analyzed serum samples obtained from 20 CDG patients and 100 controls. Results: The ratio of desialylated isoforms to total TRF was calculated for patients and controls. CDG-Type I patients showed higher amounts of bi-sialo isoform (range: 6.7–29.6%) compared to controls (<5.5%, mean percentage 3.9%). CDG-Type II pattern showed an increased peak of tri-sialo isoforms. The mean percentage of tri-sialo-TRF was 9.3% (range: 2.9–12.9%) in controls, which was lower than that obtained from two patients with COG5-CDG and MAN1B1-CDG (18.5 and 24.5%). Intraday and between-day imprecisions were less than 9 and 16%, respectively, for bi-sialo- and less than 3 and 6% for tri-sialo-TRF. Conclusions: This LC-MS-based approach provides a simple, sensitive and fast analytical tool for characterizing CDG disorders in a routine clinical biochemistry while improving diagnostic accuracy and speeding clinical decision-making.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: A new strategy implementing mass spectrometry in the diagnosis of congenital disorders of N-glycosylation (CDG) ; volume:59 ; number:1 ; year:2021 ; pages:165-171 ; extent:07 ; Clinical chemistry and laboratory medicine ; 59, Heft 1 (2021), 165-171 (gesamt 07)

Contributors, Places and Time

• Creator: Casetta, Bruno ; Malvagia, Sabrina ; Funghini, Silvia ; Martinelli, Diego ; Dionisi-Vici, Carlo ; Barone, Rita ; Fiumara, Agata ; Donati, Maria Alice ; Guerrini, Renzo ; la Marca, Giancarlo

Further information

• DOI: 10.1515/cclm-2020-0650
• URN: urn:nbn:de:101:1-2022052110325308618475
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:33 AM CEST