Related Experiment Video
Updated: Jul 15, 2025
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
DPAGT1-CDG: Report of Two New Pediatric Patients and Brief Review of the Literature
Özlem Özsoy1, Tayfun Cinleti2, Çağatay Günay1
1Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey.
Insights
This study details two patients with DPAGT1-CDG, a rare genetic disorder affecting protein glycosylation. Different DPAGT1 gene variants led to varied symptoms, highlighting the disease's complex presentation and potential treatment responses.
Area of Science:
- Genetics
- Biochemistry
- Pediatrics
Background:
- Congenital glycosylation disorders (CGDs) are a group of rare genetic diseases.
- Defects in glycoprotein and glycolipid synthesis cause CGDs, impacting multiple body systems.
- DPAGT1 gene variants lead to DPAGT1-CDG, a specific type of CGD affecting protein N-glycosylation.
Observation:
- Two patients with DPAGT1 gene variants presented with distinct clinical manifestations.
- One patient had a novel homozygous missense variant, presenting with cataracts, dysmorphic features, and epilepsy.
- The other patient had compound heterozygous variants, exhibiting later onset of muscle weakness, behavioral issues, and dysmorphic features without epilepsy.
Findings:
- Cholinesterase inhibitor therapy, specifically pyridostigmine, demonstrated effectiveness in managing muscle weakness.
- This therapeutic response supports DPAGT1 deficiency as the etiological basis for the observed symptoms.
- Comparing these cases with existing literature underscores the diverse clinical spectrum of DPAGT1-CDG.
Implications:
- The findings emphasize the importance of genetic testing for DPAGT1 variants in patients with unexplained multisystemic symptoms.
- Understanding the genotype-phenotype correlations in DPAGT1-CDG can guide diagnosis and management.
- Targeted therapies, like cholinesterase inhibitors, may offer symptomatic relief for specific manifestations of DPAGT1-CDG.
Introduction:
Congenital glycosylation disorders are multisystem diseases with heterogeneous clinical manifestations caused by defects in the synthesis of the glycan moiety of glycoproteins or glycolipids or the binding of glycans to proteins and lipids. DPAGT1 (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) is an initiating protein in the biosynthetic pathway of dolichol-linked oligosaccharides required for protein N-glycosylation. Pathogenic variants in DPAGT1 (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) gene cause a rare type of congenital glycosylation disorder called DPAGT1-CDG (formerly CDG-Ij) (OMIM #608093). It is a rare autosomal recessive disease or a milder version with congenital myasthenic syndrome known as DPAGT1-CMS. A severe disease course with hypotonia, cataracts, skeletal deformities, resistant epilepsy, intellectual disability, global developmental delay, premature death has been described in most patients with DPAGT1-CDG.
Patient Presentation:
We describe two patients with variants in the DPAGT1 gene: an 8-month-old boy with a homozygous, missense DPAGT1:c.339T>G (p.Phe113Leu) novel variant and a 13-year-old female patient with compound heterozygous variants, DPAGT1:c.466C>T (p.Arg156Cys, R156C) and DPAGT1:c.161+5G>A. While the 8-month-old patient was diagnosed with congenital cataract at the age of 1 month, had dysmorphic findings, and epilepsy, clinical symptoms in the other patient appeared later but with more prominent muscle weakness, behavioral disorder, dysmorphic findings, and no epilepsy.
Discussion:
Cholinesterase inhibitor therapy was found to be effective in patients against muscle weakness, supporting DPAGT1 deficiency as the underlying etiology. We started pyridostigmine treatment in our patient with more pronounced muscle weakness, and we saw its benefit. We aimed to present our patients diagnosed with DPAGT1-CDG due to different variants in the same gene and different clinical presentations, treatment and to compare them with other patients in the literature.
![Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62334.jpg&w=3840&q=50)