Congenital defects of glycosylation: Novel presentations with mainly neurological involvement and variable dysmorphic features

• Published in: American journal of medical genetics. Part A Vol. 185; no. 9; pp. 2739 - 2747
• Main Authors: İnci, Aslı, Cengiz, Başak, Biberoğlu, Gürsel, Okur, İlyas, Arhan, Ebru, Öner, Ali Yusuf, Kasapkara, Çiğdem Seher, Küçükçongar, Aynur, Tümer, Leyla, Ezgu, Fatih
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2021; Wiley Subscription Services, Inc
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Child; Child, Preschool; Congenital defects; congenital defects of glycosylation; Congenital Disorders of Glycosylation - complications; Congenital Disorders of Glycosylation - diagnosis; Congenital Disorders of Glycosylation - genetics; Deoxyribonucleic acid; Diagnosis; DNA; DNA sequencing; dysmorphic features; Female; Genetic disorders; Genetic Markers; Genetic screening; Glycosylation; High-Throughput Nucleotide Sequencing - methods; Humans; Inborn errors of metabolism; Infant; Isoelectric focusing; Male; Mutation; Nervous System Diseases - complications; Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; next‐generation DNA sequencing; Patients; Pediatrics; Transferrin; congenital defects of glycosylation; inborn errors of metabolism; next-generation DNA sequencing; dysmorphic features
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62247

The pathophysiology of congenital defects of glycosylation (CDG) is complex and the diagnosis has been a challenge because of the overlapping clinical signs and symptoms as well as a large number of disorders. Isoelectric focusing of transferrin has been used as a screening method but has limitations. Individual enzyme or molecular genetic tests have been difficult to perform. In this study, we aimed to describe CDG patients who were referred to from different departments either without a preliminary diagnosis or suspected to have a genetic disorder other than CDG. The patients were diagnosed mainly with a 450 gene next‐generation DNA sequencing panel for inborn errors of metabolism, which also included 25 genes for CDG. A total of 862 patients were investigated with the panel, whereby homozygous (10) or compound heterozygous (4) mutations were found in a total of 14 (1.6%) patients. A total of 13 different mutations were discovered, 10 of them being novel. Interestingly, none of the patients was suspected to have a CDG before referral. This report expands the clinical/laboratory findings in patients with CDG and stresses on the fact that CDG should be in the differential list for pediatric patients presented with nonspecific dysmorphic features and neurological delays/regression. Also, next‐generation DNA sequencing with panel approach was noticed to have a significant diagnostic potential in patients presented with nonspecific neurologic and dysmorphic findings.