{"title":"Approaches to diagnostic screening for congenital disorders of glycosylation and its prevalence in Japan.","authors":"Nobuhiko Okamoto, Machiko Kadoya, Yoshinao Wada","doi":"10.1038/s10038-025-01362-w","DOIUrl":null,"url":null,"abstract":"<p><p>Congenital disorders of glycosylation (CDG) represent an emerging and significant category within the spectrum of inborn errors of metabolism. CDG comprise a heterogeneous group of diseases caused by defects at various stages of the glycosylation pathway. Each year, new types of CDG are identified, and to date, pathogenic variants in 189 genes have been associated with over 200 distinct human glycosylation-related disorders. Each type of CDG exhibits characteristic clinical features. Many of CDG result in multisystem involvement, with the central nervous system being particularly affected. Clinical manifestations are highly variable and may include developmental delays, growth impairment, neurological abnormalities such as ataxia, hepatic dysfunction, cardiac defects, coagulation disorders, and abnormal fat distribution. In patients with unexplained neurological symptoms, it is now standard practice to include CDG in the differential diagnosis. Detection of altered glycosylation patterns in serum proteins is essential in the diagnostic evaluation of CDG. Analytical techniques allow the identification of defects in N-glycosylation, O-glycosylation, and combined glycosylation pathways. Once abnormalities in glycosylation are detected, subsequent genetic analysis is necessary to identify causative variants. Our research institute has contributed to the CDG diagnostic support center in Japan by developing novel analytical methods utilizing mass spectrometry. Through these efforts, we have facilitated the molecular diagnosis of 66 patients with CDG across Japan. In this report, we provide an overview of the current landscape of CDG in Japan, along with a summary of the screening and diagnostic processes.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s10038-025-01362-w","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Congenital disorders of glycosylation (CDG) represent an emerging and significant category within the spectrum of inborn errors of metabolism. CDG comprise a heterogeneous group of diseases caused by defects at various stages of the glycosylation pathway. Each year, new types of CDG are identified, and to date, pathogenic variants in 189 genes have been associated with over 200 distinct human glycosylation-related disorders. Each type of CDG exhibits characteristic clinical features. Many of CDG result in multisystem involvement, with the central nervous system being particularly affected. Clinical manifestations are highly variable and may include developmental delays, growth impairment, neurological abnormalities such as ataxia, hepatic dysfunction, cardiac defects, coagulation disorders, and abnormal fat distribution. In patients with unexplained neurological symptoms, it is now standard practice to include CDG in the differential diagnosis. Detection of altered glycosylation patterns in serum proteins is essential in the diagnostic evaluation of CDG. Analytical techniques allow the identification of defects in N-glycosylation, O-glycosylation, and combined glycosylation pathways. Once abnormalities in glycosylation are detected, subsequent genetic analysis is necessary to identify causative variants. Our research institute has contributed to the CDG diagnostic support center in Japan by developing novel analytical methods utilizing mass spectrometry. Through these efforts, we have facilitated the molecular diagnosis of 66 patients with CDG across Japan. In this report, we provide an overview of the current landscape of CDG in Japan, along with a summary of the screening and diagnostic processes.
期刊介绍:
The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy.
Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.