Recurrent Talaromyces Marneffei Infection Revealing X-Linked Hyper IgM Syndrome in an HIV-Negative Infant: A Diagnostic and Therapeutic Challenge

Abstract

Talaromyces marneffei (TM), a temperature-dependent dimorphic fungus and opportunistic pathogen, poses a significant threat to immunocompromised individuals, particularly in Southeast Asian regions such as China and India. This case report details an 8-month-old HIV negative Chinese infant with recurrent cough and fever, who was diagnosed with TM infection through blood culture and metagenomic next-generation sequencing (mNGS). Additionally, whole exome sequencing identified a point mutation (c.346+1G>T) in the child's CD40LG gene, primary immunodeficiency calized to chromosome position chrX:135736590, leading to X-linked Hyper IgM Syndrome (XHIGM). The patient was managed with intravenous immunoglobulin (IVIG) and a 12-day course of amphotericin B and itraconazole, which led to significant clinical improvement and discharge on a quarterly IVIG regimen. However, he required readmission for recurrent TM pneumonia at 9 and 40 months post-discharge. This case highlights the diagnostic challenge and management complexity of TM infection in the context of primary immunodeficiency.

Keywords: Talaromyces marneffei; X-linked hyper IgM syndrome; immunocompromised individuals; mNGS; primary immunodeficiency.

Figure 1

Microscopic morphology of the isolate from the patient’s blood culture. (a) Blood culture smear stained with Giemsa method under 1000× oil immersion. (b) The colony morphology was observed after 7 days of incubation at 28°C on Sabouraud agar after a positive blood culture. (c) Post-positive blood culture, fungal colony morphology was noted after 7 days’ incubation at 37°C on Sabouraud dextrose agar.

Figure 2

Genetic findings from whole-exome sequencing of the patient’s family. Whole-exome sequencing revealed the hemizygous splice-site variant c.346+1G>T in the CD40LG gene of the patient (the C→A change indicated by the arrow in the reverse trace corresponds to G→T on the forward strand), located at chrX:135736590. The sequence chromatogram showed a mutant allele burden of ~97.56% in the child. The mother was heterozygous (100% mutant reads), whereas the father was wild-type, indicating maternal origin of the mutation.

Figure 3

Chest computed tomography (CT) scans of the patient. (a) Scan obtained during the initial hospital admission. (b and c) Scans acquired during episodes of recurrent pulmonary infection at 9 months and 40 months, respectively.