Clinical Manifestations and Treatment in Korean Patients with X-Linked Agammaglobulinemia

Hannah Cho; Joong Gon Kim

doi:10.14776/piv.2017.24.3.152

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Cho and Kim: Clinical Manifestations and Treatment in Korean Patients with X-Linked Agammaglobulinemia

Original Article

Pediatric Infection & Vaccine 2017; 24(3): 152-159.

Published online: 21 December 2017

DOI: https://doi.org/10.14776/piv.2017.24.3.152

Clinical Manifestations and Treatment in Korean Patients with X-Linked Agammaglobulinemia

Hannah Cho¹, Joong Gon Kim^1,²

¹Department of Pediatrics, Seoul National University Children's Hospital, Seoul, the Republic of Korea.

²Department of Pediatrics, Seoul National University College of Medicine, Seoul, the Republic of Korea.

Corresponding author (gkim@snu.ac.kr)

Received 25 May 2017 Revised 12 July 2017 Accepted 24 July 2017

Abstract

Purpose

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The aim of this study was to investigate the clinical manifestations, molecular features, and treatment status of XLA in Korean patients at Seoul National University Children's Hospital.

Methods

Fourteen Korean boys with XLA showing serum agammaglobulinemia, non-detectable to less than 2% of peripheral B-cells, and mutation of the Btk gene were enrolled. We observed the clinical features, laboratory findings, status of treatment, and complications in these XLA patients.

Results

All XLA patients had a history of recurrent bacterial infections before diagnosis, and 20% of them had a neutropenia. Of the XLA patients 35.7% had a family history of XLA and 75% of their mothers were carriers. Btk gene analysis showed variable gene mutations in Xq22 including 9 amino acid substitutions, 3 frameshifts, 1 premature stop codon, and 1 splice defect. After intravenous immunoglobulin replacement therapy, infection episodes decreased, but complications such as bronchiectasis and chronic sinusitis remained.

Conclusions

In patients less than 4 years of age with recurrent infection, analysis of serum gamma globulin levels and the Btk gene are recommended for the early diagnosis of XLA and for the appropriate prevention of recurrent infection.

Keywords: Bruton type agammaglobulinemia, Immunoglobulins, intravenous

Figures and Tables

Fig. 1

Age at diagnosis in 14 patients with X-linked agammaglobulinemia.

Fig. 2

Bruton tyrosine kinase gene study in patient #2, his mother and sister. The mutation type was splice defect and his mother and sister were carriers.

Fig. 3

Mutation sites of Bruton's tyrosine kinase (Btk) gene in 14 patients with X-linked agammaglobulinemia. Abbreviation: UTR, untranslated region.

Table 1

Clinical Manifestation in 14 Patients with X-Linked Agammaglobulinemia

Table 2

Clinical and Laboratory Data of the 14 Patients with X-Linked Agammaglobulinemia

Abbreviations: Dx, diagnosis; AOM, acute otitis media; AGE, acute gastroenteritis; hx, history; BE, bronchiectasis; ND, not done; Ig, immunoglobulin; IVIG, intravenous immunoglobulin; Tx, treatment.

Table 3

Type of Mutation of Bruton Tyrosine Kinase Gene Detected in 14 Patients with X-Linked Agammaglobulinemia

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