Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II

Mol Genet Metab. 2017 Mar;120(3):235-242. doi: 10.1016/j.ymgme.2016.12.014. Epub 2017 Jan 3.

Abstract

Background: Congenital disorders of glycosylation (CDG) are inborn defects of glycan metabolism. They are multisystem disorders. Analysis of transferrin isoforms is applied as a screening test for CDG type I (CDG-I) and type II (CDG-II). We performed a retrospective cohort study to determine spectrum of phenotype and genotype and prevalence of the different subtypes of CDG-I and CDG-II.

Material and methods: All patients with CDG-I and CDG-II evaluated in our institution's Metabolic Genetics Clinics were included. Electronic and paper patient charts were reviewed. We set-up a high performance liquid chromatography transferrin isoelectric focusing (TIEF) method to measure transferrin isoforms in our Institution. We reviewed the literature for the rare CDG-I and CDG-II subtypes seen in our Institution.

Results: Fifteen patients were included: 9 with PMM2-CDG and 6 with non-PMM2-CDG (one ALG3-CDG, one ALG9-CDG, two ALG11-CDG, one MPDU1-CDG and one ATP6V0A2-CDG). All patients with PMM2-CDG and 5 patients with non-PMM2-CDG showed abnormal TIEF suggestive of CDG-I or CDG-II pattern. In all patients, molecular diagnosis was confirmed either by single gene testing, targeted next generation sequencing for CDG genes, or by whole exome sequencing.

Conclusion: We report 15 new patients with CDG-I and CDG-II. Whole exome sequencing will likely identify more patients with normal TIEF and expand the phenotypic spectrum of CDG-I and CDG-II.

Keywords: Combined N- and O-glycosylation; Congenital disorders of glycosylation; N-glycosylation; Transferrin isoelectric focusing.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Congenital Disorders of Glycosylation / classification*
  • Congenital Disorders of Glycosylation / diagnosis*
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / metabolism
  • Exome
  • Female
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Infant
  • Male
  • Phenotype
  • Protein Isoforms / metabolism
  • Retrospective Studies
  • Sequence Analysis, DNA / methods*
  • Transferrin / metabolism*

Substances

  • Protein Isoforms
  • Transferrin