Intellectual disability and bleeding diathesis due to deficient CMP–sialic acid transport

Mohamed, Miski; Ashikov, Angel; Guillard, Maïlys; Robben, Joris H.; Schmidt, Samuel; Heuvel, Bert van den; Brouwer, Arjan P.M. de; Gerardy‐Schahn, Rita; Deen, Peter M.T.; Wevers, Ron A.; Lefeber, Dirk; Morava, Éva

doi:10.1212/wnl.0b013e3182a08f53

Cited by 43 publications

(45 citation statements)

References 27 publications

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“…Sera of patients with a defect in one of the nucleotidesugar transporters SLC35A1, SLC35A2, or SLC35C1 were subsequently analyzed. For the recently described CMP-sialic acid transporter defect, SLC35A1-CDG, 34 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 loss of sialic acids was easily detectable by the peaks at 78,975 and 79,266 Da (Fig 2, C) corresponding to an accumulation of disialylated transferrin and trisialylated transferrin. For the defect in the SLC35A2, as recently described (SLC35A2-CDG 35 ), a low level of truncated glycans was observed that lacked incorporation of galactoses.…”

Section: Q16mentioning

confidence: 99%

High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation

Scherpenzeel

Steenbergen

Morava

et al. 2015

Translational Research

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Section: Q16mentioning

confidence: 99%

High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation

Scherpenzeel

Steenbergen

Morava

et al. 2015

Translational Research

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“…Other recently defined recognizable CDGs are MAN1B1-CDG, characterized by intellectual disability (ID) with speech delay, dysmorphic features, and truncal obesity (Scherpenzeel et al 2014) (Fig. 2c and d); and SLC35A1-CDG, presenting with conotruncal malformation, ID, bleeding diathesis, and renal disease (Mohamed et al 2013). …”

Section: Clinical Phenotype and Recognizable Phenotypes In Cdgs Involmentioning

confidence: 99%

“…This autosomal recessive sialic-acid-transporter disorder, previously labeled CDG-IIf, has been redefined as a CDG with multisystem disease and secretory glycosylation anomalies (Mohamed et al 2013). The single previously described case showed no abnormality in transferrin pattern and isolated macrothrombocytopathy, and pancytopenia as the single presentation of the abnormal cytidine monophosphate sialic acid (CMP-sialic acid) transport (Martinez-Duncker et al 2005).…”

Section: Newly Discovered Cdgs Involving N-linked Glycosylationmentioning

confidence: 99%

Congenital disorders of glycosylation: new defects and still counting

Scott

Gadomski

Kozicz

et al. 2014

J of Inher Metab Disea

111

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Almost 50 inborn errors of metabolism have been described due to congenital defects in N-linked glycosylation. These phenotypically diverse disorders typically present as clinical syndromes, affecting multiple systems including the central nervous system, muscle function, transport, regulation, immunity, endocrine system, and coagulation. An increasing number of disorders have been discovered using novel techniques that combine glycobiology with next-generation sequencing or use tandem mass spectrometry in combination with molecular gene-hunting techniques. The number of “classic” congenital disorders of glycosylation (CDGs) due to N-linked glycosylation defects is still rising. Eight novel CDGs affecting N-linked glycans were discovered in 2013 alone. Newly discovered genes teach us about the significance of glycosylation in cell–cell interaction, signaling, organ development, cell survival, and mosaicism, in addition to the consequences of abnormal glycosylation for muscle function. We have learned how important glycosylation is in posttranslational modification and how glycosylation defects can imitate recognizable, previously described phenotypes. In many CDG subtypes, patients unexpectedly presented with long-term survival, whereas some others presented with nonsyndromic intellectual disability. In this review, recently discovered N-linked CDGs are described, with a focus on clinical presentations and therapeutic ideas. A diagnostic approach in unsolved N-linked CDG cases with abnormal transferrin screening results is also suggested.

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“…Hematologic defects and susceptibility to infections were reverted by oral supplementation with Fuc [42]. By comparison, mutations in the CMP-Sia transporter gene SLC35A1 were found in a patient with intellectual impairment, seizures, ataxia, thrombocytopenia, renal and cardiac disorders [43]. A general conclusion about the role of sialylation cannot be drawn from these two cases, but the symptoms confirm the importance of Sia for leukocyte and platelet functions.…”

Section: Localization Of Donor Substratesmentioning

confidence: 99%

Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction

Hennet

Cabalzar

2015

Trends in Biochemical Sciences

108

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Glycosylation is a ubiquitous modification of lipids and proteins. Despite the essential contribution of glycoconjugates to the viability of all living organisms, diseases of glycosylation in humans have only been identified over the past few decades. The recent development of next-generation DNA sequencing techniques has accelerated the pace of discovery of novel glycosylation defects. The description of multiple mutations across glycosylation pathways not only revealed tremendous diversity in functional impairments, but also pointed to phenotypic similarities, emphasizing the interconnected flow of substrates underlying glycan assembly. The current list of 100 known glycosylation disorders provides an overview of the significance of glycosylation in human development and physiology. Congenital disorders of glycosylation -a consice chart of glycocalyx dysfunctionThierry Hennet, Jürg Cabalzar Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland AbstractGlycosylation is a ubiquitous modification of lipids and proteins. Despite the essential contribution of glycoconjugates to the viability of all living organisms, diseases of glycosylation in humans have only been identified over the past few decades. The recent development of next-generation DNA sequencing techniques has accelerated the pace of discovery of novel glycosylation defects. The description of multiple mutations across glycosylation pathways has revealed a tremendous diversity of functional impairments bus also pointed to phenotypic similarities emphasizing the interconnected flow of substrates underlying glycan assembly. The current list of 100 known glycosylation disorders provides an overview on the significance of glycosylation in human development and physiology. Highlights Congenital disorders underline the role of glycosylation in human development.  Next-gen sequencing techniques expanded the discovery of glycosylation gene defects.  The clinical variability of glycosylation disorders implies they are underdiagnosed. Glycosylation disordersGlycosylation is by far the most complex form of protein [1,2] and lipid modification [3,4] in all domains of life. The tremendous diversity of glycoconjugate structures resulting from intricate biosynthetic pathways is a major factor hampering the assignment of functions to glycans chains. Much has been learnt from the study of disrupted glycosylation genes in model organisms, thereby establishing numerous essential contributions of glycans in regulating cell and organ functions [5]. The study of human diseases of glycosylation brings additional insights by providing a more differentiated view on glycan functions. Indeed, most human mutations are hypomorphic, thus causing partial loss of glycosylation reactions that lead to variable clinical manifestations.Diseases of glycosylation are also referred to as congenital disorders of glycosylation (CDG). Given the heterogeneity of glycans, the clinical scope of CDG is considerable, ranging from nearly normal phenotypes to sever...

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Intellectual disability and bleeding diathesis due to deficient CMP–sialic acid transport

Cited by 43 publications

References 27 publications

High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation

High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation

Congenital disorders of glycosylation: new defects and still counting

Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction

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