Normal transferrin patterns in congenital disorders of glycosylation with Golgi homeostasis disruption: apolipoprotein C-III at the rescue!

Raynor, Alexandre; Vincent‐Delorme, Catherine; Alaix, Anne-Sophie; Cholet, Sophie; Vuillaumier‐Barrot, Sandrine; Fenaille, François; Besmond, Claude; Bruneel, Arnaud

doi:10.1016/j.cca.2021.05.016

Cited by 6 publications

(2 citation statements)

References 29 publications

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“…The diagnosis is usually based on genetic testing, after finding a type 1 serum transferrin isoelectrofocusing pattern 31 . Although the serum transferrin profile could be normal in the first weeks of life in CDG patients 32 or CDG patients with Golgi disruption 33 this has been reported abnormal in ALG1‐CDG patients in early childhood. However, the possibility of spontaneous improvement in transferrin glycosylation in young PMM2‐CDG patients is known 34 …”

Section: Discussionmentioning

confidence: 99%

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

Bosnyak,

Sadek,

Ranatunga

et al. 2024

JIMD Reports

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ALG1‐CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N‐acetylglucosamine (GlcNAc2)‐pyrophosphate (PP)‐dolichol to the growing oligosaccharide chain, resulting in impaired N‐glycosylation of proteins. N‐glycosylation has a key role in functionality, stability, and half‐life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3‐year‐old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1‐CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysis of highly glycosylated proteins in fibroblasts revealed decreased intercellular adhesion molecule 1 (ICAM1), but normal lysosomal associated membrane protein 1 and 2 (LAMP1 and LAMP2) expression levels. Glycoproteomics in fibroblasts showed the presence of the abnormal tetrasacharide. Reviewing the literature, we found 86 reported ALG1‐CDG patients, but only one with normal transferrin analysis. Based on our results we would like to highlight the importance of multiple approaches in diagnosing ALG1‐CDG, as normal serum transferrin glycosylation or other biomarkers with normal expression levels can occur.

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Section: Discussionmentioning

confidence: 99%

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

Bosnyak,

Sadek,

Ranatunga

et al. 2024

JIMD Reports

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“…1,[9][10][11] However, in some cases, hyposialylation is observed in the O-glycans but not in N-glycans, emphasizing the importance of the analysis of O-glycans. 12) In 2012, matrix-assisted laser desorption/ionization (MALDI) MS enabled rapid analysis without the prior separation of apoCIII from serum was reported. 13,14) MS is superior to IEF in that it distinguishes non-glycosylated apoCIII isoforms from those containing neutral glycans.…”

Section: Introductionmentioning

confidence: 99%

Electrospray Ionization Mass Spectrometry of Apolipoprotein CIII to Evaluate <i>O</i>-glycan Site Occupancy and Sialylation in Congenital Disorders of Glycosylation

Wada

Okamoto

2022

Mass Spectrometry

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Congenital disorders of glycosylation (CDG) are inherited metabolic diseases that a ect the synthesis of glycoconjugates. Defects in mucin-type O-glycosylation occur independently or in combination with N-glycosylation disorders, and the pro ling of the O-glycans of apolipoprotein CIII (apoCIII) by mass spectrometry (MS) can be used to support a diagnosis. e biomarkers are site occupancy and sialylation levels, which are indicated by the content of non-glycosylated apoCIII0a isoform and by the ratio of monosialylated apoCIII1 to disialylated apoCIII2 isoforms, respectively. In this report, electrospray ionization (ESI) quadrupole MS of apoCIII was used to identify these biomarkers. Among the instrumental parameters, the declustering potential (DP) induced the fragmentation of the O-glycan moiety including the r-GalNAc linkage, resulting in an increase in apoCIII0a ions. is incurs the risk of creating a false positive for reduced site occupancy. e apoCIII1/apoCIII2 ratio was substantially unchanged despite some dissociation of sialic acids. erefore, appropriate DP settings are especially important when transferrin, which requires a higher DP, for N-glycosylation disorders is analyzed simultaneously with apoCIII in a single ESI MS measurement. Finally, a reference range of diagnostic biomarkers and mass spectra of apoCIII obtained from patients with SLC35A1-, TRAPPC11-, and ATP6V0A2-CDG are presented.

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

Harvey

2024

Mass Spectrometry Reviews

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The use of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry for the analysis of carbohydrates and glycoconjugates is a well‐established technique and this review is the 12th update of the original article published in 1999 and brings coverage of the literature to the end of 2022. As with previous review, this review also includes a few papers that describe methods appropriate to analysis by MALDI, such as sample preparation, even though the ionization method is not MALDI. The review follows the same format as previous reviews. It is divided into three sections: (1) general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation, quantification and the use of computer software for structural identification. (2) Applications to various structural types such as oligo‐ and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals, and (3) other general areas such as medicine, industrial processes, natural products and glycan synthesis where MALDI is extensively used. Much of the material relating to applications is presented in tabular form. MALDI is still an ideal technique for carbohydrate analysis, particularly in its ability to produce single ions from each analyte and advancements in the technique and range of applications show little sign of diminishing.

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Normal transferrin patterns in congenital disorders of glycosylation with Golgi homeostasis disruption: apolipoprotein C-III at the rescue!

Cited by 6 publications

References 29 publications

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

Electrospray Ionization Mass Spectrometry of Apolipoprotein CIII to Evaluate <i>O</i>-glycan Site Occupancy and Sialylation in Congenital Disorders of Glycosylation

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

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