Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Hyper-IgE syndromes: reviewing PGM3 deficiency

Yang, Linlin; Fliegauf, Manfred; Grimbacher, Bodo

doi: 10.1097/MOP.0000000000000158

Purpose of review The hyper-IgE syndromes have been recognized as a group of primary immunodeficiencies characterized by eczema, recurrent skin and lung infections, and elevated serum IgE. Recently, mutations in phosphoglucomutase 3 (encoding PGM3, which is involved in the protein glycosylation pathway) have been identified in autosomal recessive forms of hyper-IgE syndromes.

Recent findings Autosomal recessive, hypomorphic PGM3 mutations cause a multisystem disorder, characterized by both a congenital glycosylation disease and a hyper-IgE syndrome. The reported mutations in PGM3 led to an impaired biosynthesis of UDP-GlcNAc and impaired tri-antennary and tetra-antennary N-glycan structures. Laboratory results in patients showed eosinophilia, a T-cell proliferation defect, and a reversed CD4/CD8 ratio. The impaired glycosylation in PGM3-mutant patients will not only affect proteins involved in the immune system, and thus causes a multisystem phenotype.

Summary The identification of hyper-IgE syndromes-associated mutations in PGM3 provides the basis for future studies on the pathophysiology and the molecular mechanisms of eczema, IgE dysregulation, and increased susceptibility to infections.

Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany

Correspondence to Bodo Grimbacher, MD, Center for Chronic Immunodeficiency, University Medical Center Freiburg, Engesser Straße 4, 79108 Freiburg, Germany. Tel: +49 761 270 77731; fax: +49 761 270 77744; e-mail:,

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins