bims-meglyc 2026-06-28 papers

Issue of 2026–06–28
two papers selected by
Silvia Radenkovic, UMC Utrecht

Biomolecules. 2026 Jun 16. pii: 885. [Epub ahead of print]16(6):

Glycogen and Glycosylation: Friends or Foes?

Rohit Sai Reddy Konada, James Osborn, Sharmistha Mitra.

Glycosylation, glycogen metabolism, and ubiquitination represent three fundamental cellular processes that are traditionally studied as distinct aspects of biology. Glycosylation and glycogen metabolism are unique carbohydrate-based pathways. The process of glycosylation generates structurally diverse glycans that regulate protein folding, cell signaling, and host-pathogen interactions, while glycogen serves as a glucose reserve essential for energy homeostasis. Emerging evidence reveals a deep mechanistic connection between these pathways, particularly in the context of brain biology and inherited metabolic diseases. Here, we present recent research linking glycosylation defects with glycogen metabolism, highlighting how changes in the shared metabolites and enzymatic pathways contribute to human health and disease. We then discuss the overlapping disease symptoms of congenital disorders of glycosylation and glycogen storage diseases, with particular emphasis on polyglucosan body-forming diseases. We also highlight the role of non-canonical ubiquitin ligase complexes such as laforin-malin and LUBAC and present emerging evidence for their potential role in the glycogen quality-control mechanism. Finally, we review current therapeutic strategies for CDGs and GSDs, including monosaccharide supplementation, glycogen synthase modulation, and gene therapy. Together, this review underscores glycogen as more than an energy store-as a key contributor to glycosylation homeostasis and cellular regulation in health and disease.

Keywords: LUBAC; N-linked; O-linked; glucose; glycans; glycogen; polyglucosan body; ubiquitin

DOI: https://doi.org/10.3390/biom16060885

Mol Genet Metab. 2026 Jun 23. pii: S1096-7192(26)00478-6. [Epub ahead of print]148(4): 110195

Expanding the clinical and molecular spectrum of NGLY1 deficiency: A multicenter cohort.

BACKGROUND: NGLY1 deficiency is an ultra-rare multisystem disorder characterized by developmental delay, hyperkinetic movement disorder, hypo-/alacrimia, peripheral neuropathy, and elevated transaminases.
METHODS: We conducted a multicenter retrospective study including 15 patients from 11 families to evaluate the clinical, biochemical, and molecular features of the disease. A literature review was also performed, and phenotypic data from published patients were evaluated.
RESULTS: All patients presented with developmental delay and dysmorphic facial features. Common neurological findings included abnormal EEG (10/15), seizures (9/15), hyperkinetic movement disorder (8/15), reduced deep tendon reflexes (6/15), and peripheral neuropathy (3/5). Frequent non-neurological features included feeding difficulties (9/15), scoliosis (7/13), hypo-/alacrimia (6/15), constipation (6/15), and auditory neuropathy (2/4). Peripheral and auditory neuropathy findings were observed over time. Elevated transaminases were the most common laboratory abnormality (12/14) and were transient in most patients (9/12), followed by low total cholesterol (7/10) and HDL levels (5/10). We identified 10 distinct variants, including two novel variants c.629delA (p.(Lys210SerfsTer14)) and c.1036C > T (p.(Gln346Ter)). Most patients carried homozygous variants, and no clear genotype-phenotype correlation was observed.
CONCLUSION: Our findings expand the clinical and molecular spectrum of NGLY1 deficiency and highlight its dynamic and progressive course, supporting the need for long-term clinical follow-up. NGLY1 deficiency may be considered in patients with neurologic findings and dysmorphic features, especially when transient elevated transaminases and hypolipidemia are also present.

Keywords: Congenital disorder of deglycosylation; Developmental delay; Dysmorphic features; Hypolipidemia; NGLY1 deficiency; Transient elevated transaminases

DOI: https://doi.org/10.1016/j.ymgme.2026.110195