# Insights into ALG3-CDG: A case study combining glycan profiling and genetic analysis

## TL;DR

This case study identifies ALG3-CDG in a child with developmental issues by combining glycan profiling and genetic analysis.

## Contribution

The study demonstrates the diagnostic value of integrating glycan profiling with genetic sequencing in rare CDG cases.

## Key findings

- Abnormal N-glycan profile with truncated mannosylated structures was detected in the patient's serum.
- Whole exome sequencing identified compound heterozygous variants in the ALG3 gene confirming ALG3-CDG.
- The case underscores the importance of combined glycan and genetic approaches for diagnosing CDG.

## Abstract

Congenital disorders of glycosylation (CDG) are a group of rare metabolic disorders caused by the defects in the glycosylation pathways of biomacromolecules leading to altered glycoprofiles in affected individuals. In this case study, we present a 3-year-old Slovak male patient with developmental delay, hearing impairment, epilepsy, microcephaly, facial dysmorphism, corpus callosum dysgenesis, and cardiac abnormalities. To elucidate the underlying cause, we performed LC-ESI-MS analysis of RapiFluor-labelled N-glycans released from blood serum glycoproteins. The results revealed an abnormal N-glycan profile, characterized by an increased relative abundance of truncated mannosylated structures (Hex3HexNAc2 and Hex4HexNAc2) and a decreased presence of higher-order mannose structures (Hex6-8HexNAc2). A molecular analysis was also conducted. Whole exome sequencing confirmed a diagnosis of ALG3-CDG with compound heterozygous variants: c.165C > T (p.Gly55=) and c.1060C > T (p.Arg354Cys) in the ALG3 gene, encoding alpha-1,3-mannosyltransferase in the endoplasmic reticulum. This presented case highlights the importance of glycan profiling and genetic analysis in diagnosing congenital disorders of glycosylation, facilitating early intervention and management.