Congenital disorders of glycosylation: New defects and still counting

Kyle Scott, Therese Gadomski, Tamas Kozicz, Eva Morava-Kozicz

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)609-617
Number of pages9
JournalJournal of Inherited Metabolic Disease
Volume37
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Congenital Disorders of Glycosylation
Glycosylation
Glycomics
Inborn Errors Metabolism
Muscles
Endocrine System
Mosaicism
Post Translational Protein Processing
Transferrin
Tandem Mass Spectrometry
Cell Communication
Intellectual Disability
Genes
Polysaccharides
Immunity
Cell Survival
Central Nervous System
Phenotype
Survival

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Congenital disorders of glycosylation : New defects and still counting. / Scott, Kyle; Gadomski, Therese; Kozicz, Tamas; Morava-Kozicz, Eva.

In: Journal of Inherited Metabolic Disease, Vol. 37, No. 4, 01.01.2014, p. 609-617.

Research output: Contribution to journalArticle

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