bims-meglyc 2026-01-18 papers

Issue of 2026–01–18
five papers selected by
Silvia Radenkovic, UMC Utrecht

Pediatr Transplant. 2026 Jan;30(1): e70266

PMM2-CDG and the Role of Liver Transplantation as a Long-Term Solution: A Case Report.

Brianna A Blasingame, Amy Yang, Pamela L Valentino, Monica Penon-Portmann, Christina Lam, Maria Cristina Pacheco, Henry Lin.

BACKGROUND: Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG) is the most common congenital disorder of glycosylation, affecting protein glycosylation across multiple organ systems. Hepatic involvement may range from isolated elevations in liver transaminases to end-stage liver disease. Reported outcomes of liver transplantation as a treatment modality are sparse.
CASE REPORT: We describe one of the first reported cases of liver transplantation in a child with PMM2-CDG and interim post-transplant outcomes. This patient was diagnosed at 4 months of age after presenting with failure to thrive, lipodystrophy, hypotonia, developmental delay, elevated transaminases, hypoalbuminemia, and coagulopathy. He developed cirrhosis and portal hypertension as well as sequelae of poor protein glycosylation. All these included coagulopathy, protein-losing enteropathy, and refractory ascites requiring serial intravenous fresh frozen plasma and furosemide. He ultimately underwent a liver transplant, after which his ascites resolved. Post-transplant, he developed new-onset recurrent pericardial effusions, suspected to be from a viral etiology versus extrahepatic manifestations of PMM2-CDG, and elevated transaminases following transplantation.
DISCUSSION/CONCLUSIONS: Liver transplantation may offer clinical benefit in PMM2-CDG with severe hepatic involvement, including resolution of ascites and improved quality of life, due to its potential to restore liver glycosylation function. However, this is only a partial correction as persistent extrahepatic manifestations underscore the need for further research into transplant outcomes and systemic disease progression in CDG.

Keywords: Liver transplant CDG; congenital disorder of glycosylation; liver transplant

DOI: https://doi.org/10.1111/petr.70266

Pediatr Int. 2026 Jan-Dec;68(1):68(1): e70324

Cerebral blood flow and benzodiazepine receptor distribution in a patient with ALG6-congenital disorder of glycosylation.

Ryuki Matsuura, Kenjiro Kikuchi, Azusa Oba, Hirofumi Ohashi, Nobuhiko Okamoto.

Keywords: ALG6‐CDG; SPECT imaging; benzodiazepine receptor distribution; brain magnetic resonance imaging; congenital disorders of glycosylation

DOI: https://doi.org/10.1111/ped.70324

Mol Genet Metab. 2026 Jan 08. pii: S1096-7192(26)00010-7. [Epub ahead of print]147(3): 109727

L-fucose supplementation in a patient with global hypofucosylation and a mono-allelic variant in SLC35C1: Clinical improvement and assessment of biomarkers.

Rodrigo T Starosta, Miao He, Sara Gracie, Janell Kierstein, Christian Thiel, Nastassja Himmelreich, Yupeng Liu, Wenyue Zhang, Andrew C Edmondson, Naomi Meeks, Austin Larson, Johan L K Van Hove, Aaina Kochhar.

Fucosylation disorders are rare types of congenital disorders of glycosylation (CDG), the most common being SLC35C1-CDG, which is classically described as a leukocyte adhesion deficiency (hence the previous name of "leukocyte adhesion deficiency type II") with dysmorphic features, short stature, and moderate-to-severe developmental and intellectual disabilities. In more recent years, several cases have been described of individuals with bi-allelic SLC35C1 variants and biochemical proof of hypofucosylation who had short stature, dysmorphic features, and intellectual disability, but no hematological abnormalities. In this article, we report a patient with growth faltering, neuroirritability, nystagmus, developmental delays, microcephaly, dysmorphic features, and hypogammaglobulinemia G. Biochemical investigations including serum N-glycan profiling, fucosylation-focused whole serum glycoprotein profiling, and serum lectin blots, all of which showed significant global hypofucosylation. Exome sequencing revealed a single likely pathogenic variant, SLC35C1 (NM_018389.4):c.503_505delTCT, p.(Phe168del), which was inherited from an unaffected mother. Whole genome sequencing with manual review of raw data did not reveal any second pathogenic variants; SLC35C1 mRNA sequencing was negative for changes in the second allele or allelic imbalance. The patient was started on L-fucose supplementation, with subsequent improvements in weight and head circumference, normalization of IgG levels, and remarkable developmental catch-up. Biochemically, there was an increase in abundance of previously decreased fucosylated glycan species in serum, especially Fuc1GlcNAc2Man3 (a glycan that is known to be enriched in neutrophils). In summary, we present here further evidence for the role of L-fucose supplementation in treating hypofucosylation disorders and suggest that IgG and fucosylated glycan species may be useful as biomarkers in this scenario, although further research is needed to validate them as such. It is likely that the early introduction of L-fucose in this patient may have led to the excellent developmental outcomes observed.

Keywords: CDG; Congenital disorder of glycosylation; Fucose; Fucosylation; GDP-fucose transporter; Time-of-flight mass spectrometry

DOI: https://doi.org/10.1016/j.ymgme.2026.109727

Mol Biol Rep. 2026 Jan 14. 53(1): 288

Disorders of sex development associated with MPI and RSPH1 variants expand the phenotypic spectrum of CDG and PCD in Morocco.

Houda Harmak, Salaheddine Redouane, Adil El Hamouchi, Hicham Charoute, Ouafaa Aniq Filali, Rachid Aboutaieb, Abdelhamid Barakat, Hassan Rouba.

BACKGROUND: Human sex development is a highly regulated process guiding undifferentiated gonads toward a testicular or ovarian fate. Disruptions in this pathway result in disorders of sexual development (DSD), characterized by atypical chromosomal, gonadal, or anatomical sex. These conditions usually appear as ambiguous genitalia at birth or as atypical pubertal development during adolescence. Different etiologic, phenotypic, and genotypic factors can cause DSD. Advances in next-generation sequencing (NGS) have significantly accelerated the identification of genetic variants through targeted panels, including both known genes involved in sex determination and differentiation, as well as newly discovered genes linked to DSD.
METHODS AND RESULTS: In this study, whole exome sequencing (WES) was performed on a Moroccan patient, born to non-consanguineous parents, who presented with severe hypospadias, micropenis, and cryptorchidism, and exhibited overlapping phenotypic features consistent with congenital disorder of glycosylation (CDG) and primary ciliary dyskinesia (PCD). After variant annotation and prioritization, two heterozygous variants in the MPI (c.305 C > T; p. Ser102Leu) and RSPH1 (c.471 C > G; p. His157Gln) genes were identified and confirmed by Sanger sequencing in family members. Their pathogenic effects on protein structures and functions were subsequently anticipated using bioinformatic tools and molecular dynamics (MD) simulations.
CONCLUSIONS: To our knowledge, this is the first report of these specific variants in the context of DSD, shedding light on a unique genotype-phenotype profile associated with the patient's complex clinical presentation. The high genetic variability underlying these disorders has made molecular diagnosis challenging. Yet, genomic approaches could expand our understanding of DSD landscape and improve diagnosis, personalized interventions, and patient management.

Keywords: MPI ; RSPH1 ; Congenital disorder of glycosylation (CDG); Disorders of sexual development (DSD); Molecular dynamics (MD); Moroccan patient; Primary ciliary dyskinesia (PCD); Whole exome sequencing (WES)

DOI: https://doi.org/10.1007/s11033-026-11449-y

Trends Cell Biol. 2026 Jan 14. pii: S0962-8924(25)00265-X. [Epub ahead of print]

Expanding roles of N-glycosylation in the endoplasmic reticulum.

Mengxiao Ma, Rajat Rohatgi.

N-linked glycosylation in the endoplasmic reticulum (ER), catalyzed by two oligosaccharyltransferase (OST) complexes, has long been viewed as a constitutive post-translational modification. Recent discoveries suggest that OST complexes play a much more plastic and directive role in regulating ER processes. Here, we review this work and focus on one specific mechanism that uses N-glycosylation to regulate the stability of the ER chaperone HSP90B1. This degradative process regulates the cell-surface abundance of multiple signaling receptors that are HSP90B1 clients: toll-like receptors, WNT receptors, and growth factor receptors. This unusual system enables the status of ER-based processes to influence the sensitivity of cells to extracellular signals, with implications for tissue growth and development, inflammation, and immune function.

Keywords: chaperone; endoplasmic reticulum; glycosylation; oligosaccharyltransferase; signaling receptor; translation

DOI: https://doi.org/10.1016/j.tcb.2025.12.001