PID in Disguise: Molecular Diagnosis of IRAK-4 Deficiency in an Adult Previously Misdiagnosed With Autosomal Dominant Hyper IgE Syndrome

J Clin Immunol. 2015 Nov;35(8):739-44. doi: 10.1007/s10875-015-0205-x. Epub 2015 Oct 15.

Abstract

Autosomal recessive IL-1R-associated kinase 4 (IRAK-4) deficiency is a rare cause of recurrent pyogenic infections with limited inflammatory responses. We describe an adult female patient with severe lung disease who was phenotypically diagnosed as suffering from autosomal dominant Hyper IgE syndrome (AD HIES) because of recurrent skin infections with Staphylococcus aureus, recurrent pneumonia and elevated serum IgE levels. In contrast to findings in AD HIES patients, no abnormalities were found in the Th17 and circulating follicular helper T cell subsets. A panel-based sequencing approach led to the identification of a homozygous IRAK4 stop mutation (c.877C > T, p.Gln293*).

Keywords: IRAK-4; Primary immunodeficiency; hyper IgE syndrome; next-generation sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Diagnosis, Differential
  • Diagnostic Errors
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoglobulin E / blood
  • Immunologic Deficiency Syndromes / diagnosis*
  • Immunologic Deficiency Syndromes / genetics
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Interleukin-6 / metabolism
  • Job Syndrome / diagnosis*
  • Pathology, Molecular
  • Pneumonia / diagnosis*
  • Primary Immunodeficiency Diseases
  • Sequence Deletion / genetics
  • Skin / immunology
  • Skin / microbiology
  • Staphylococcal Infections / diagnosis*
  • Staphylococcus aureus
  • Th17 Cells / immunology*

Substances

  • Interleukin-6
  • Immunoglobulin E
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases

Supplementary concepts

  • IRAK4 Deficiency