Publications | CDG Hub

November 2025

November 5, 2025

Structural characterization of zebrafish Ngly2, an ovary-enriched acid PNGase required for egg free glycan production

Honda, A et al. J Biol Chem., November 5, 2025

Peptide:N-glycanase (PNGase) is a deglycosylating enzyme acting on asparagine(N)-linked glycans on glycoproteins. It is well established that fish possesses two PNGases with distinct properties. One is a cytosolic PNGase (NGLY1 in human), active at neutral pH and widely conserved among eukaryotes. The other is called acid PNGase and found in fish embryos; it is active at acidic pH and is believed to be of lysosomal origin. The gene encoding the acid PNGase has not been identified in animals, and its evolutionary distribution has remained unknown. In this study, we identified the gene encoding the acid PNGase, which we named Ngly2, in zebrafish (Danio rerio).

November 3, 2025

Novel PGM1 Mutation in Congenital Disorder of Glycosylation Type 1T: A Case Report of Liver Failure and Myopathy

Al-Ahmari AA. Am J Case Rep., November 3, 2025

We report a 20-month-old boy, born to consanguineous parents, who initially received a misdiagnosis of galactosemia following abnormal newborn screening. Despite dietary modifications, he developed persistent transaminitis, coagulopathy, hypotonia, and delayed motor milestones. Further evaluation revealed abnormal carbohydrate-deficient transferrin analysis, and whole exome sequencing identified a homozygous PGM1 variant of uncertain significance, supporting CDG Type 1T diagnosis.

November 1, 2025

ATP6AP2-Related Disease Caused by Splicing Defects: Abnormal Glycosylation and the First Affected Female

Raynor A, et al. J Inherit Metab Dis., November 1, 2025

ATP6AP2 splicing variants cause syndromic X-linked intellectual disability Hedera type (XPDS; OMIM#300423) and X-linked parkinsonism with spasticity (MRXSH; OMIM#300911). Alternatively, ATP6AP2 missense variants lead to hepatopathy, immunological abnormalities, cutis laxa and only mild intellectual disability with N-/O-glycosylation defects (ATP6AP2-CDG; OMIM#301045). The disparity between neurological and hepatic ATP6AP2-related disease entities is an ongoing puzzle. We aimed to investigate whether patients with an isolated neurological presentation of ATP6AP2-related disease, consistent with XPDS/MRXSH, also have abnormal glycosylation biomarkers, potentially implicating this as part of the pathological mechanism.

October 2025

October 28, 2025

Oral D-mannose therapy during pregnancy in a woman with MPI-CDG: A case report and management review

Martzolff L, et al. Mol Genet Metab., October 28, 2025

Mannose 6-phosphate isomerase deficiency is a rare disorder of N-glycosylation leading to impaired coagulation, enteropathy, hypoglycemia and liver disease. D-mannose is the only available treatment. We report the case of a pregnant woman with MPI-CDG and the management of D-mannose therapy during pregnancy.

October 24, 2025

AAV9-mediated NGLY1 gene replacement suppresses non-epileptic convulsions in Ngly1-/- rats

sahina M, Fujinawa R, Hirayama H, Yukitake H, Suzuki T. Biochem Biophys Res Commun., October 24, 2025

N-glycanase 1 (NGLY1) deficiency is a rare autosomal-recessive neurological disorder characterized by neurological dysfunction and so far, has no effective therapy. A systemic Ngly1-/- rat model recapitulates many patient symptoms, including developmental delay, motor and cognitive deficits. Here we carried out further detailed phenotypic analyses for the Ngly1-/- rats, with particular focus on those easily translatable to patients' symptoms, i.e. sleep disturbances, EEG abnormalities and convulsive behaviors. EEG/EMG recordings revealed fragmented sleep and frequent spontaneous epileptiform discharges in Ngly1-/- rats. Continuous video-EEG monitoring confirmed a high incidence of convulsive events with/without epileptic discharge. At three weeks of age, Ngly1-/- rats received a single intracerebroventricular injection of AAV9-hNGLY1. We then examined whether central nervous system-targeted gene therapy using an adeno-associated virus serotype 9 carrying human NGLY1 (AAV9-hNGLY1) can rescue those phenotypes

October 24, 2025

Clinical utility of untargeted urine oligosaccharide screening.

Pino GB, et al. Mol Genet Metab., October 24, 2025

High-resolution urine oligosaccharide screening with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been clinically available for 10 years and has been used to help diagnose a wide spectrum of disorders. The untargeted nature of MALDI-TOF MS analysis gives it broad clinical utility. Here we report characteristic profiles for several disorders that had not previously been described using this method, including lysosomal disorders, congenital disorders of glycosylation, and glycogen storage disorders. In addition, we review the clinical performance of the assay in our laboratory and provide basic test performance information for each condition.

October 24, 2025

Novel SSR4 gene splice variant leads to congenital disorder of glycosylation, type Iy

Li N, Chen C. Front Pediatr., October 24, 2025

Congenital disorders of glycosylation (CDG) are a group of multi-systemic genetic disorders. Over 100 monogenic human diseases were known related with defects in glycosylation process. Defects of SSR4 gene lead to a rare X linked pattern of CDG which has been rarely reported. We reported a Chinese boy with developmental delay, microcephaly, and epileptic seizures. Whole exome sequencing and Sanger sequencing were performed in the family. A novel maternal splice variant c.351+1del in SSR4 gene was identified by trio-exome sequencing, and confirmed by Sanger sequencing.

October 23, 2025

Atypical Phenotype of Predominant Autoimmune Cytopenia and Impaired Perforin Expression in XMEN Syndrome

Grombirikova H, et al. J Immunol Res., October 23, 2025

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is caused by a pathogenic variant in the magnesium transporter 1 (MAGT1) gene. The defect leads to impaired N-glycosylation which affects various immune processes. In this study, we described the disease course, clinical features and laboratory parameters observed in six patients from three families diagnosed with XMEN syndrome

October 22, 2025

STT3A is essential for Wnt signaling and represents a target for cancers driven by RNF43 deficiency

He Z, et al. Cell Chem Biol., October 22, 2025

Abnormalities in the Wnt pathway are major drivers of cancer. RNF43 loss-of-function mutations are frequently detected in aggressive cancers lacking targeted therapies, underscoring the need to uncover key regulators and targets of this pathway. Using a double death trap (DDT) Wnt reporter and genome-wide CRISPR screen, we identified STT3A as an essential regulator of Wnt signaling.

October 21, 2025

In vitro cell model to dilucidate the underlying molecular mechanism associated with ophthalmic manifestation of congenital disorders of glycosylation: studying an ALG2-CDG patient

Cubilla MA, Sclausero AC, Bisbal M, Asteggiano CG. Front Genet., October 21, 2025

In this study, we utilized the 661W cell line to explore the molecular consequences of a homozygous variant in the ALG2 gene (c.752G>T; p.Arg251Leu), which encodes the enzyme α-1,3-mannosyltransferase. Following transfection with a plasmid carrying the variants of the gene of interest ALG2 p.Arg251/p.Arg251, we carefully evaluated changes in gene expression using RT-PCR and Western blotting. Our results suggest that the 661W cell line may serve as a useful model for examining the potential impact of a specific mutation, supporting a possible link between the mutation's molecular effects and clinical disease progression.