NGLY1 Deficiency

  • Global developmental delay
  • Intellectual diability
  • Hypotonia
  • Hypo- or alacrima

Eye Findings

  • Hypolacrima (83%)
  • Incomplete or abnormal blink (73%)
  • Optic disc abnormalities (73%)
    • Peripapillary atrophy, cupping
  • Corneal abnormalities typically found with dry eye
    • punctate epithelial erosions
    • pannus and neovascularization
  • Conjunctival injection (60%)
  • Strabismus (33%)
    • Exotropia > Esotropia
    • Restricted ocular movements
  • Iris abnormalities
    • Reduced pupillary reactivity (47%)
    • Irregular iris (27%)
  • Nystagmus- rare

Other Findings

  • Increased liver transaminases
  • Polyneuropathy

Etiology

  • Autosomal Recessive
  • Loss-of-function variants of the NGLY1 encoding N-glycanase 1
    • an enzyme that removes the sugar moiety from proteins
    • cleaves N-glycans to generate deglycosylated proteins and oligosaccharides containing 1-amino-GlcNac
    • degrades misfolded proteins in the endoplasmic reticulum

Resources