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Review
. 2024 Feb 12:14:1341236.
doi: 10.3389/fcimb.2024.1341236. eCollection 2024.

Assistance of next-generation sequencing for diagnosis of disseminated Bacillus Calmette-Guerin disease with X-SCID in an infant: a case report and literature review

Haiyang Zhang  1   2 , Yi Liao  2   3 , Zhensheng Zhu  4 , Hanmin Liu  1   2 , Deyuan Li  1   2 , Sisi Wang  1   2
Affiliations
Review

Assistance of next-generation sequencing for diagnosis of disseminated Bacillus Calmette-Guerin disease with X-SCID in an infant: a case report and literature review

Haiyang Zhang et al. Front Cell Infect Microbiol. .

Abstract

Bacille Calmette-Guérin (BCG) is a live strain of Mycobacterium bovis (M.bovis) for use as an attenuated vaccine to prevent tuberculosis (TB) infection, while it could also lead to an infection in immunodeficient patients. M.bovis could infect patients with immunodeficiency via BCG vaccination. Disseminated BCG disease (BCGosis) is extremely rare and has a high mortality rate. This article presents a case of a 3-month-old patient with disseminated BCG infection who was initially diagnosed with hemophagocytic syndrome (HPS) and eventually found to have X-linked severe combined immunodeficiency (X-SCID). M.bovis and its drug resistance genes were identified by metagenomics next-generation sequencing (mNGS) combined with targeted next-generation sequencing (tNGS) in blood and cerebrospinal fluid. Whole exome sequencing (WES) revealed a pathogenic variant in the common γ-chain gene (IL2RG), confirming X-SCID. Finally, antituberculosis therapy and umbilical cord blood transplantation were given to the patient. He was successfully cured of BCGosis, and his immune function was restored. The mNGS combined with the tNGS provided effective methods for diagnosing rare BCG infections in children. Their combined application significantly improved the sensitivity and specificity of the detection of M.bovis.

Keywords: Bacillus Calmette-Guérin; immunodeficiency; next-generation sequencing; vaccine; whole exome sequencing.

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Conflict of interest statement

Author ZZ is employed by Hugobiotech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The chest CT revealed the absence of a thymus.
Figure 2
Figure 2
The treatment timeline of the patient.
Figure 3
Figure 3
Diagnosis of MTB infection using mNGS. (A) The reads mapped to the MTB genome with coverage of 14.8487% in the blood. The distribution of species-specific reads aligns with the MTB in the blood. (B) The reads mapped to the MTB genome with coverage of 29.1761% in the CSF. The distribution of species-specific reads aligns with the MTB in the CSF.
Figure 4
Figure 4
Genetic detection of the variant in the IL2RG gene (Exon 3: c.391C>T; p.Gln131Ter) among the patient, his father (wild-type) and his mother (carrier).
See this image and copyright information in PMC

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