Epidemiology of congenital disorders of glycosylation (CDG)—overview and perspectives

Abstract

Background and aim Congenital disorders of glycosylation (CDG) are a large heterogeneous group of about 170 rare inherited metabolic disorders due to defective protein and lipid glycosylation. This study aimed to assemble and summarise available data on the epidemiology of CDG. Methods A set of keywords related to epidemiology and CDG was defined. The keywords were combined through a custom Python script, search through the MEDLINE database, using PubMed as the search engine. The script retrieved the correspondent MEDLINE data from each article, and the relevant information was exported. Next, inclusion and exclusion criteria were set and applied during the selection phase. Finally, epidemiology-related information was extracted and compiled. Results One hundred sixty-five papers on CDG epidemiology were included in this literature review. Most of them reported on the frequency of symptoms in CDG patients followed in cohort studies, on pathogenic variant allelic frequency, and on the prevalence of the disorder in populations. According to this review, the most reported CDG was phosphomannomutase-2 deficiency (PMM2-CDG) followed in descending order by FKTN-CDG, EXT1/EXT2-CDG, ALG6-CDG, and PIGA-CDG. Conclusions We provide an overview on epidemiological data regarding 93 CDG by compiling information from the literature. Generating epidemiological data on CDG is important to appropriately target resources for CDG research and drug development and to support public health decision-making.

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review

“…Our comprehensive literature review shows that immunological events in PMM2-CDG, mostly represented as increased susceptibility to infection, are prevalent during infancy and childhood and occasionally lead to severe, sometimes fatal, outcomes. Our review data highlighted that immunologically affected patients predominantly have R141H-bearing genotypes, in line with previous reports ( 128 , 168 ) and probably because the R141H genetic variant is the most prevalent pathogenic PMM2 variant ( 30 , 217 ). Yet, the limited evidence per genotype hampers the establishment of genotype-phenotype correlations.…”

Novel insight into FCSK‐congenital disorder of glycosylation through a CRISPR‐generated cell model

“…(Hullen et al., 2021 ; Lefeber et al., 2011 ) It is notable that four of the five known types of fucosylation defects have been discovered quite recently, (Hullen et al., 2021 ) and it cannot be ignored that more cases will be identified after describing a disorder. Given FCSK‐CDG specifically, it is noteworthy that three of the five reported patients have Middle Eastern ancestry, (Al Tuwaijri et al., 2023 ; Manoochehri et al., 2022 ; Ng, Rosenfeld, et al., 2018 ; Ozgun & Sahin, 2022 ) which is well explainable by the recessive inheritance nature of this disease and the high rate of consanguineous marriage in some nations in the Middle East and Western Asia (Piedade et al., 2022 ). Since these are generally less‐developed countries, a high underdiagnosis of FCSK‐CDG and other fucosylation‐related CDGs with autosomal recessive inheritance is expected.…”

The multifaceted roles of the brain glycogen

“…Indeed, aortic stiffness in PD is caused by advanced glycan formation in aortic smooth muscle (Wens et al, 2014). Furthermore, multiple GSD and CDG patients share many neurological symptoms, including epilepsy and cognitive impairment (Korlimarla et al, 2019; Nitschke et al, 2018; Piedade et al, 2022). While the novel route of hexosamine metabolism in the brain provides a direct metabolic connection between glycogen and N‐glycans, key insights remain to be determined.…”