Congenital Disorders of Glycosylation: What Clinicians Need to Know?

Patryk Lipiński,Anna Tylki-Szymańska

doi:10.3389/fped.2021.715151

Abstract

Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous disorders characterized by defects in the synthesis of glycans and their attachment to proteins and lipids. This manuscript aims to provide a classification of the clinical presentation, diagnostic methods, and treatment of CDG based on the literature review and our own experience (referral center in Poland). A diagnostic algorithm for CDG was also proposed. Isoelectric focusing (IEF) of serum transferrin (Tf) is still the method of choice for diagnosing N-glycosylation disorders associated with sialic acid deficiency. Nowadays, high-performance liquid chromatography, capillary zone electrophoresis, and mass spectrometry techniques are used, although they are not routinely available. Since next-generation sequencing became more widely available, an improvement in diagnostics has been observed, with more patients and novel CDG subtypes being reported. Early and accurate diagnosis of CDG is crucial for timely implementation of appropriate therapies and improving clinical outcomes. However, causative treatment is available only for few CDG types.

Highlights

Congenital disorders of glycosylation (CDG), previously known as carbohydrate-deficient glycoprotein syndromes, constitute a group of inborn errors of metabolism (IEM) characterized by impaired synthesis and attachment of glycans to glycoproteins and glycolipids and impaired synthesis of glycosylphosphatidylinositol
CDG types are classified into defects in protein N-glycosylation, protein Oglycosylation, glycosphingolipid, and glycosylphosphatidylinositol (GPI) anchor glycosylation defects, and multiple glycosylation pathway defects [1,2,3,4]
This manuscript aims to provide a classification of the clinical presentation, diagnostic methods, and treatment of CDG based on the literature review and our own experience

Summary

BACKGROUND

Congenital disorders of glycosylation (CDG), previously known as carbohydrate-deficient glycoprotein syndromes, constitute a group of inborn errors of metabolism (IEM) characterized by impaired synthesis and attachment of glycans to glycoproteins and glycolipids and impaired synthesis of glycosylphosphatidylinositol. More than 150 CDG subtypes have been reported, while the phosphomannomutase-2 deficiency (PMM2-CDG) comprises the most common one [1,2,3,4]. CDG types are classified into defects in protein N-glycosylation, protein Oglycosylation, glycosphingolipid, and glycosylphosphatidylinositol (GPI) anchor glycosylation defects, and multiple glycosylation pathway defects [1,2,3,4]. CDG nomenclature is denoted by the affected gene name (non-italicized) followed by -CDG (i.e., PMM2-CDG, phosphomannomutase-2 deficiency) [1,2,3,4]. Most CDG types are autosomal recessive in inheritance, but autosomal dominant (i.e., EXT1/EXT2-CDG, GANAB-CDG, PRKCSH-CDG, POGLUT1-CDG, POFUT1-CDG) as well as X-linked (i.e., ALG13-CDG, PIGA-CDG, SLC35A2-CDG, ATP6AP1-CDG) forms have been described [1,2,3,4]

CLINICAL PRESENTATION

Findings

DIAGNOSTIC PROCESS