Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation

Mol Genet Metab. 2019 Aug;127(4):368-372. doi: 10.1016/j.ymgme.2019.07.001. Epub 2019 Jul 9.


Background: NGLY1-CDDG is a congenital disorder of deglycosylation caused by a defective peptide:N-glycanase (PNG). To date, all but one of the reported patients have been diagnosed through whole-exome or whole-genome sequencing, as no biochemical marker was available to identify this disease in patients. Recently, a potential urinary biomarker was reported, but the data presented suggest that this marker may be excreted intermittently.

Methods: In this study, we performed untargeted direct-infusion high-resolution mass spectrometry metabolomics in seven dried blood spots (DBS) from four recently diagnosed NGLY1-CDDG patients, to test for small-molecule biomarkers, in order to identify a potential diagnostic marker. Results were compared to 125 DBS of healthy controls and to 238 DBS of patients with other diseases.

Results: We identified aspartylglycosamine as the only significantly increased compound with a median Z-score of 4.8 (range: 3.8-8.5) in DBS of NGLY1-CDDG patients, compared to a median Z-score of -0.1 (range: -2.1-4.0) in DBS of healthy controls and patients with other diseases.

Discussion: The increase of aspartylglycosamine can be explained by lack of function of PNG. PNG catalyzes the cleavage of the proximal N-acetylglucosamine residue of an N-glycan from the asparagine residue of a protein, a step in the degradation of misfolded glycoproteins. PNG deficiency results in a single N-acetylglucosamine residue left attached to the asparagine residue which results in free aspartylglycosamine when the glycoprotein is degraded. Thus, we here identified aspartylglycosamine as the first potential small-molecule biomarker in DBS for NGLY1-CDDG, making a biochemical diagnosis for NGLY1-CDDG potentially feasible.

Keywords: Aspartylglycosamine; Biomarker; NGLY1-CDDG; Peptide:N-glycanase.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives*
  • Acetylglucosamine / blood
  • Adolescent
  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Congenital Disorders of Glycosylation / blood
  • Congenital Disorders of Glycosylation / diagnosis*
  • Dried Blood Spot Testing
  • Female
  • Humans
  • Infant
  • Male
  • Mass Spectrometry
  • Mutation
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / blood
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / deficiency*


  • Biomarkers
  • N-acetylglucosaminylasparagine
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Acetylglucosamine

Supplementary concepts

  • NGLY1 deficiency