2026 Clinician Corner - A rare case of TCF3-related agammaglobulinemia in a child with recurrent Haemophilus influenzae bacteremia

Abstract 

We report a case of a previously healthy 4-year-old girl who presented with two recurrent episodes of complicated pneumonia and Haemophilus influenzae bacteremia. Immunologic evaluation revealed hypogammaglobulinemia, as immunoglobulins (IgG, IgA, IgM, IgE) were below detectable levels and genetic testing identified a pathogenic TCF3 variant, confirming a diagnosis of TCF3 (transcription factor 3) deficiency. TCF3 is a key transcription factor in B- and T-cell development, and its deficiency results in impaired antibody production and increased susceptibility to infections. This case highlights the rarity of TCF3 mutations in pediatric patients, the importance of early recognition, and the critical role of immunoglobulin replacement therapy as the current mainstay of treatment.     

Keywords:  bacteremia; immunodefiency; TCF3 deficiency; transcription factor 3

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Faculty credentials/disclosure 

The planners and faculty for this activity have no relevant financial relationships to disclose. The patient consented to the publication of this report.

Process

Click the "add to cart/begin" button, pay any relevant fee, take the quiz, complete the evaluation, and claim your CME credit.  You must achieve 100% on the quiz with unlimited attempts available.

  • By completing this process, you are attesting that you have read the journal article.

Expiration date:

Credit eligibility for this article is set to expire on January 1, 2027.

Learning Objectives

After completing the article, the learner should be able to:

  • Understand how agammaglobulinemia is generally diagnosed. 
  • Understand that TCF3 mutation deficiency has variable clinical presentations. 
  • Describe common management strategies. 

Key Points 

  • TCF3 is a transcription factor essential for B-cell development, class-switch recombination, and antibody production. 

  • Current treatment is supportive, with immunoglobulin replacement and infection prophylaxis being the mainstays of management, as no curative therapy exists. 

  • TCF3 deficiency is a rare immunodeficiency and has variable clinical presentations, with only a handful of pediatric cases reported in the literature. 

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Course summary
Available credit: 
  • 1.00 American Board of Surgery (ABS) Accredited CME
    Successful completion of this CME activity enables the learner to earn credit toward the CME requirement of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.
  • 1.00 AMA PRA Category 1 Credit™
    The A. Webb Roberts Center for Continuing Medical Education of Baylor Scott & White Health is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
  • 1.00 Attendance
Course opens: 
01/01/2026
Course expires: 
01/01/2027
Cost:
$25.00

Yi Fang, DOa, and Gueorgui Dubrocq, MDb 

 

a Department of Pediatric Hospital Medicine, Baylor Scott & White McLane Children’s Hospital, Temple, Texas, USA 

b Department of Pediatric Infectious Disease, Baylor Scott & White McLane Children’s Hospital, Temple, Texas, USA 

 

Corresponding author: Gueorgui Dubrocq, MD, Baylor Scott & White McLane Children’s Hospital, 1901 SW H.K. Dodgen Loop, Building 300, MS-CK-400, Temple, TX 76592 (e-mail: [email protected]) 

The planners and faculty for this activity have no relevant financial relationships to disclose. The authors report no funding. The patient consented to publication of this case report. 

Accreditation

The A. Webb Roberts Center for Continuing Medical Education of Baylor Scott & White Health is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Designation

AMA PRA Category 1 Credit™

The A. Webb Roberts Center for Continuing Medical Education of Baylor Scott & White Health designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ABS CC

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Available Credit

  • 1.00 American Board of Surgery (ABS) Accredited CME
    Successful completion of this CME activity enables the learner to earn credit toward the CME requirement of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.
  • 1.00 AMA PRA Category 1 Credit™
    The A. Webb Roberts Center for Continuing Medical Education of Baylor Scott & White Health is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
  • 1.00 Attendance

Price

Cost:
$25.00
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