bims-meglyc 2026-02-15 papers

Issue of 2026–02–15
three papers selected by
Silvia Radenkovic, UMC Utrecht

Cureus. 2026 Jan;18(1): e101202

Early Diagnosis and Targeted Therapy in SLC39A8-Congenital Disorder of Glycosylation: A Case Report From Bulgaria.

Valentina Varbanova, Genoveva Tacheva, Teodora Paneva, Marina Krasteva, Dimitar Stamatov, Ivan Litvinenko.

SLC39A8-congenital disorder of glycosylation (SLC39A8-CDG) is a rare autosomal recessive metabolic disease of manganese transport, leading to defective glycosylation and mitochondrial dysfunction. An eight-month-old male infant with severe hypotonia, developmental delay, and dystonic episodes was initially misdiagnosed as epilepsy. Genetic testing identified a homozygous pathogenic variant in the SLC39A8 gene, and biochemical analysis confirmed low manganese levels. Upon initiation of oral manganese sulfate therapy, the patient demonstrated significant clinical improvement, including the achievement of new motor milestones. To our knowledge, this is the first documented case in Bulgaria. This case underscores the importance of early genetic diagnosis and targeted metabolic treatment in altering the clinical trajectory of SLC39A8-CDG. Timely recognition allows for intervention in a disorder that, despite its rarity, has a modifiable course and potential for meaningful developmental gains.

Keywords: congenital disorder of glycosylation; dystonia; global developmental delay; hypotonia; manganese transportation; slc39a8-cdg

DOI: https://doi.org/10.7759/cureus.101202

Ophthalmic Genet. 2026 Feb 10. 1-8

Clinical, biochemical and genetic characterization of an Egyptian patient with SRD5A3-congenital glycosylation disorder.

Caroline Atef Tawfik, Raghda Zaitoun, Sahar Sabry, Mona Lofti Essawi, Nagham Elbagoury.

PURPOSE: To characterize an undiagnosed patient with retinal dystrophy, ataxia, and neurodevelopmental delay.
MATERIALS AND METHODS: A 13-year-old female patient presenting with nystagmus and defective vision since infancy, underwent ophthalmological, neurological examination, ultra-wide field fundus photography, autofluorescence and electroretinogram. Exome sequencing (ES) was done followed by segregation analysis. Analysis of the glycosylation profiles of plasma glycoprotein markers was performed using immunoblotting.
RESULTS: Visual acuity was counting fingers; her fundus examination and imaging revealed an Early Childhood Onset Retinal Dystrophy (ECORD) phenotype. Ichthyosiform skin lesions were noted, and neurological assessment revealed proximal limb-girdle pattern of weakness, hyperactive reflexes, extensor plantar responses with evidence of cerebellar dysfunction. ES uncovered a homozygous, likely pathogenic missense variant c.509A > G, p.(Tyr170Cys) in SRD5A3 gene. In silico functional analysis prediction tools supported the variant being deleterious. Segregation analysis confirmed carrier status of parents and the brother, while plasma glycoprotein markers for N- and O-glycosylation showed an aberrant glycosylation profile.
CONCLUSION: We report a variant in the SRD3A5 gene reported for the first time in a case of CDG. We are expanding the neurophenotypic spectrum by reporting proximal limb-girdle pattern of weakness combined with diffusely brisk reflexes and bilateral extensor plantar responses suggestive of corticospinal or neuromuscular axis involvement.

Keywords: Congenital Disorder of Glycosylation; SRD3A5; exome sequencing; glycosylation profile; secretory protein panel

DOI: https://doi.org/10.1080/13816810.2026.2623106

Cell Tissue Res. 2026 Feb 02. 403(2): 15

Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.

Ebru Ada, Volkan Seyrantepe.

Neu1 (lysosomal sialidase 1) is essential for removing sialic acid from oligosaccharides and glycoconjugates. Neu1 deficiency impairs lysosomal digestion, leading to sialidosis and sialoglycoprotein accumulation. It also increases lipids, including gangliosides GM3, GD3, GM4, and LM1, in the kidney, liver, and spleen. Neu1-/- mice display symptoms resembling Type II sialidosis, including enlarged spleen and liver, kidney issues, neurological problems, spinal defects, and oligosaccharide buildup. The study examined secondary lipid alterations and inflammation in the cortex and cerebellum of these mice. Lipidomic, molecular, and immunohistochemical analyses of tissues from 2 and 5 M Neu1-/- mice revealed reduced levels of lipids, including PC, PE, PS, and CL, along with increased pro-inflammatory cytokines and loss of oligodendrocytes and neurons. Signs of astrogliosis and microgliosis emerged in specific brain regions. These results indicate that reduced levels of glycerophospholipids could serve as an indicator of inflammation in sialidosis mice. Future research should investigate therapies targeting these lipid changes, as modulating glycerophospholipids might slow disease progression in sialidosis patients.

Keywords: Mouse model; Neu1 sialidase; Neuroinflammation; Secondary lipids

DOI: https://doi.org/10.1007/s00441-026-04045-w