AUTHOR=Zhang Haiyang , Liao Yi , Zhu Zhensheng , Liu Hanmin , Li Deyuan , Wang Sisi 

TITLE=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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1341236

DOI=10.3389/fcimb.2024.1341236

ISSN=2235-2988

ABSTRACT=<p><italic>Bacille Calmette-Guérin</italic> (BCG) is a live strain of <italic>Mycobacteriu</italic>m <italic>bovis</italic> (<italic>M.bovis</italic>) for use as an attenuated vaccine to prevent <italic>tuberculosis</italic> (TB) infection, while it could also lead to an infection in immunodeficient patients. <italic>M.bovis</italic> 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). <italic>M.bovis</italic> 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 (<italic>IL2RG</italic>), 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 <italic>M.bovis</italic>.</p>