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

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.

• Authors: Amal Al Teneiji, Theodora U J Bruun, Sarah Sidky, Dawn Cordeiro, Ronald D Cohn, Roberto Mendoza-Londono, Mahendranath Moharir, Julian Raiman, Komudi Siriwardena, Lianna Kyriakopoulou, Saadet Mercimek-Mahmutoglu
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 120 Issue 3 Pg. 235-242 (03 2017) ISSN: 1096-7206 [Electronic] United States
• PMID: 28122681 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Chemical References

• Protein Isoforms
• Transferrin

Topics

• Adolescent
• Child
• Child, Preschool
• Chromatography, High Pressure Liquid
• Congenital Disorders of Glycosylation (classification, diagnosis, genetics, 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)