ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients

Hum Mutat. 2016 Jul;37(7):653-60. doi: 10.1002/humu.22983. Epub 2016 Mar 21.


Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder.

Keywords: CDG; asparagine-linked glycosylation protein 1; carbohydrate-deficient transferrin; xeno-tetrasaccharide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / metabolism
  • Congenital Disorders of Glycosylation / genetics*
  • Congenital Disorders of Glycosylation / metabolism
  • Female
  • Genes, Lethal
  • Glycosylation
  • Humans
  • Male
  • Mannosyltransferases / genetics*
  • Mutation*
  • Polysaccharides / metabolism*
  • Sequence Analysis, DNA
  • Survival Analysis


  • Biomarkers
  • Polysaccharides
  • Mannosyltransferases
  • chitobiosyldiphosphodolichol beta-mannosyltransferase