bims-meglyc Biomed News
on Metabolic disorders affecting glycosylation
Issue of 2026–05–17
two papers selected by
Silvia Radenkovic, UMC Utrecht
  1. Mandibular Distraction Osteogenesis in Monozygotic Twins With Structural-Dominant ALG8 Variants.
  2. Natural history of NGLY1 deficiency: motor function & clinical features.
  1. J Craniofac Surg. 2026 May 08.
    Mandibular Distraction Osteogenesis in Monozygotic Twins With Structural-Dominant ALG8 Variants.
    Xingyu Xia, Shigui Lu, Jinlong Zou, Chuanzhi Wang, Weimin Shen.
      Biallelic ALG8 mutations typically manifest as lethal multisystem congenital disorders of glycosylation (CDG-Ih). We report a unique case of monozygotic female twins presenting with Pierre Robin sequence (PRS) and orofacial-digital (OFD)-like features (cleft lip, tongue hamartomas, digital anomalies) without classic metabolic crises. Whole-exome sequencing identified compound heterozygous variants (c.140C>T and c.1349+1G>A). Severe airway obstruction was successfully managed through bilateral mandibular distraction osteogenesis (MDO), achieving complete respiratory weaning and oral feeding. This report provides critical evidence that specific ALG8 defects can manifest as a structural-dominant "metabolic ciliopathy," expanding the known phenotypic spectrum. Crucially for the craniofacial surgeon, this finding proves that MDO remains a safe, life-saving intervention even in complex genetic-metabolic backgrounds, providing a vital management precedent where theoretical risks of coagulation and bone metabolic issues might otherwise deter surgical intervention.
    Keywords:  ALG8; Pierre Robin sequence; congenital disorders of glycosylation; mandibular distraction osteogenesis
    DOI:  https://doi.org/10.1097/SCS.0000000000012872
  2. Hum Mol Genet. 2026 May 11. pii: ddag013. [Epub ahead of print]35(8):
    Natural history of NGLY1 deficiency: motor function & clinical features.
    Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter.
      N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen participants, representing roughly 10% of the total identified patient population, were enrolled to complete three onsite visits. Participants in this study exhibited phenotypes previously reported, including core disease phenotypes, hypotonia, scoliosis, musculoskeletal abnormalities, abnormal electroencephalogram (EEG) results, and visual and genitourinary abnormalities. Results from validated neurocognitive and motor function assessments revealed profound global developmental delays in all participants, including communication, gross and fine motor function, and cognitive domains. Age-equivalent scores identified a widening developmental gap between participants and neurotypical peers over time, indicating delayed milestone achievement and/or regression. Although fluctuations were observed, measurements for individual participants were mostly stable over the course of the NHS. Liver transaminase and biomarker N-acetylglucosamine-asparagine (GlcNAc-Asn; GNA) levels were elevated in all participants. Results build on previous studies and inform the selection of potential endpoints for emerging interventional clinical trials, including laboratory values, neurocognitive and motor function assessments, and caregiver reported outcomes.
    Keywords:  Global developmental delay; Motor function; N-glycanase 1; NGLY1 Deficiency; Natural History Study
    DOI:  https://doi.org/10.1093/hmg/ddag013
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