Acute liver failure in a male patient with NGLY1-congenital disorder of deglycosylation

Eur J Med Genet. 2020 Aug;63(8):103952. doi: 10.1016/j.ejmg.2020.103952. Epub 2020 May 15.


Congenital disorder of N-linked deglycosylation (CDDG, MIM 615273) is a very rare autosomal recessive disorder caused by pathogenic variants in the NGLY1 gene. Transient transaminitis is the typical hepatic dysfunction described in these patients, but also included neonatal jaundice, hepatomegaly, splenomegaly, and steatosis. Microscopically, intrahepatic cytoplasmic inclusions and fibrosis are seen. We report a five-year-old male patient who presented a severe episode of acute liver failure (ALF). Exome sequencing identified compound heterozygous pathogenic/likely pathogenic variants in the NGLY1 gene: NM_018297.3:c.1891del, p.(Gln631Serfs*7) in exon 12 and NM_018297.3:c.531dup, p.(Asn178Glnfs*9) in exon 4. Serology for the most frequent viral hepatitis infections, autoimmune panel, and investigations for metabolic or toxic causes were also normal or negative. Hepatic disease resolved favorably after 46 days. Liver function tests and elastography remains normal after a 2-year follow-up. This is the first report of a reversible ALF among patients with NGLY1-CDDG. Although its definitive cause remains unknown, we suggest a direct relation between liver disease and mitochondrial respiratory chain damage in the context of impaired NGLY1 gene function. Further reports are required in order to know the long-term prognosis of ALF in patients with NGLY1-CDDG.

Keywords: Acute liver failure; Cirrhosis; Congenital disorder of deglycosylation; Liver fibrosis; NGLY1.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Congenital Disorders of Glycosylation / complications
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / pathology*
  • Humans
  • Liver / pathology
  • Liver Failure, Acute / etiology*
  • Liver Failure, Acute / pathology
  • Male
  • Mutation
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics*


  • NGLY1 protein, human
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase