- Marked multisystemic phenotypic variability with predominant hypotonia, global developmental delay, epilepsy, and characteristic MRI findings such as cerebral atrophy and white matter abnormalities.
- Conventional biochemical screening is insufficient: transferrin isoelectric focusing was normal in nearly half the cases despite pathogenic variants, contributing to underdiagnosis.
- Early molecular testing is essential for diagnosis, reveals rare CDG subtypes and novel genotype-phenotype correlations, and should be integrated into workup.
Pediatr Neurol. 2026 Sep 23;185:89-94. doi: 10.1016/j.pediatrneurol.2026.09.015. Online ahead of print.
ABSTRACT
BACKGROUND: Congenital disorders of glycosylation (CDG) comprise a diverse group of rare inherited metabolic diseases caused by defects in glycan biosynthesis and processing. Since glycoconjugates play a critical role in development and cellular integrity, disruptions in glycosylation can result in a wide range of multisystemic symptoms, often with prominent neurological involvement. Despite their clinical relevance, many CDG cases remain underdiagnosed due to the limited sensitivity of conventional biochemical tests. This study aims to further characterize the clinical, radiologic, and genetic findings.
METHODS: This study retrospectively analyzed nine pediatric patients diagnosed with CDG at a tertiary center. Clinical features, biochemical investigations, neuroimaging findings, and molecular genetic results were reviewed. Genetic confirmation was obtained using targeted next-generation sequencing or whole-exome sequencing.
RESULTS: The cohort revealed wide phenotypic variability, with predominant features including hypotonia, global developmental delay, epilepsy, and abnormal brain magnetic resonance imaging findings such as cerebral atrophy and white matter abnormalities. While transferrin isoelectric focusing revealed abnormal patterns in five patients, four patients had normal transferrin isoelectric focusing results despite harboring pathogenic variants. Several rare CDG subtypes were identified, including GALNT2-CDG, B4GALT1-CDG, and ST3GAL5-CDG.
CONCLUSIONS: Our study underscores the importance of considering CDG in the differential diagnosis of multisystemic neurodevelopmental disorders. It also highlights the limitations of regular biochemical screening in excluding CDG, emphasizing the essential role of early implementation of molecular testing. Our findings not only contribute to the expanding spectrum of CDG presentations in pediatric populations but also provide valuable insights into novel genotype-phenotype correlations.
PMID:42854636 | DOI:10.1016/j.pediatrneurol.2026.09.015
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