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Volume 48, Number 1, February 2015

X-linked hyper-IgM syndrome with CD40LG mutation: Two case reports and literature review in Taiwanese patients 

Hu-Yuan Tsai, Hsin-Hui Yu, Yin-Hsiu Chien, Kuan-Hua Chu, Yu-Lung Lau, Jyh-Hong Lee, Li-Chieh Wang, Bor-Luen Chiang, Yao-Hsu Yang

Received: November 28, 2011    Revised: May 16, 2012    Accepted: July 9, 2012   


Corresponding author:

* Corresponding author. Department of Pediatrics, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 10002, Taiwan.
E-mail address: (Y.-H. Yang). 


Background and purpose: 

Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case. 


Key words:

CD40 ligand, Hyper-IgM syndrome, Immunodeficiency