Abstract
Severe Combined Immunodeficiency (SCID) is a rare, life-threatening primary immunodeficiency disorder characterized by defective T- and B-cell function. Early diagnosis is crucial to prevent fatal infections. We report a case of a 10-month-old female with persistent fever, leukocytosis, and lymphopenia, ultimately diagnosed with SCID. This case highlights the diagnostic challenges and importance of early recognition.
Introduction
SCID is a group of genetic disorders leading to profound immune dysfunction. Affected infants present with recurrent, persistent, and severe infections. This case emphasizes the role of hematological parameters, particularly persistent leukocytosis with lymphopenia, as an early clue for SCID.
Case Presentation
A 10-month-old female presented with a two-month history of persistent fever, poor weight gain, and recurrent respiratory tract infections. Despite multiple courses of antibiotics, the fever persisted. Family history was unremarkable.
On examination, the child was irritable, febrile (38.5°C), and tachypneic. There was no lymphadenopathy or hepatosplenomegaly. Her weight was below the third percentile for age.
Investigations
- Complete blood count (CBC):
- Leukocytosis (Total Leukocyte Count: 35,000/µL)
- Absolute lymphocyte count: 400/µL (lymphopenia)
- Flow cytometry: Absent CD3+ T cells, markedly reduced CD19+ B cells, normal NK cells.
- Serum immunoglobulins: Markedly reduced IgG, IgA, and IgM.
- Lymphocyte proliferation assay: Absent response to mitogens.
- Genetic analysis: Confirmed mutation in the IL2RG gene, consistent with X-linked SCID.
- CT Chest: Granulomatous lesion noted.
Diagnosis
Based on clinical presentation, persistent lymphopenia, absent T-cell function, and genetic confirmation, a diagnosis of SCID was established. The baby had received the Bacillus Calmette-Guérin (BCG) vaccine at birth, which is relevant given the granulomatous lesion on imaging.
Management and Outcome
The patient was started on prophylactic antimicrobials, antifungals, and intravenous immunoglobulin (IVIG). Bone marrow transplant (BMT) was planned as definitive therapy. Despite supportive treatment, the patient succumbed to sepsis before BMT could be performed.
Discussion
SCID is a pediatric emergency. Persistent lymphopenia (<1,500/µL in infants) is a key diagnostic clue. Leukocytosis with lymphopenia, as seen in our case, can be misleading and delay diagnosis. Newborn screening for SCID and early hematopoietic stem cell transplantation significantly improve outcomes. The presence of a granulomatous lesion post-BCG vaccination suggests the potential for disseminated BCG infection, a well-documented complication in SCID patients.
Conclusion
This case underscores the importance of recognizing persistent leukocytosis with lymphopenia as a potential marker of SCID. Early diagnosis and intervention are crucial in improving survival. Special attention should be given to infants receiving BCG vaccination, as it may unmask underlying immunodeficiency disorders.
References
- Notarangelo LD, Kim MS, Walter JE, Lee YN. Human RAG mutations: biochemistry and clinical implications. Nat Rev Immunol. 2016;16(4):234-246.
- Shearer WT, Dunn E, Notarangelo LD, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in the United States. JAMA. 2015;314(7):729-738.
- Bousfiha A, Jeddane L, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38(1):129-143.
Keywords: SCID, persistent fever, leukocytosis, lymphopenia, primary immunodeficiency, case report, BCG vaccine, granulomatous lesion
