Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature

Eur J Med Genet. 2024 Feb:67:104895. doi: 10.1016/j.ejmg.2023.104895. Epub 2023 Dec 7.


Introduction: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.

Case presentation: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years. Appetite loss, motor and cognitive decline became evident at age 12 years. Electrophysiological studies identified paroxysmal discharges on myoclonic seizure and a giant somatosensory evoked potential. Perampanel was effective for controlling myoclonic seizures. Exome sequencing revealed that the patient carried compound heterozygous variants in NGLY1, NM_018297.4: c.857G > A and c.-17_12del, which were inherited from mother and father, respectively. A literature review confirmed that myoclonic seizures were observed in 28.5% of patients with epilepsy. No other patients had progressive myoclonic epilepsy or cognitive decline in association with loss-of-function variations in NGLY1.

Conclusion: Our data provides evidence that a group of patients with CDDG1 manifest slowly progressive myoclonic epilepsy and cognitive decline during the long-term clinical course.

Keywords: Congenital disorder of deglycosylation (CDDG); Deterioration; NGLY1; Progressive myoclonic epilepsy (PME); Somatosensory evoked potential (SEP).

Publication types

  • Review
  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Congenital Disorders of Glycosylation*
  • Epilepsies, Myoclonic* / drug therapy
  • Epilepsies, Myoclonic* / genetics
  • Humans
  • Male
  • Mutation
  • Myoclonic Epilepsies, Progressive* / genetics
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / deficiency*
  • Phenotype
  • Seizures


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

Supplementary concepts

  • NGLY1 deficiency