Updated: 5/13/2019

Severe Combined Immunodeficiency

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Snapshot
  • A 1-month old baby girl is brought into the pediatrician’s office for failure to thrive. The patient has had multiple episodes of diarrhea, once requiring an inpatient admission at age 2 weeks. She has also had 2 episodes of ear infections and 1 episode of bronchiolitis. Her family history includes a sibling who died at age 2 months of bacterial pneumonia. On physical exam, there decreased weight and height for her age, dehydration, and thrush. She has diffuse alopecia and flaky rash on her scalp. All immunoglobulin levels except IgG are low. Flow cytometry is sent to evaluate for immunodeficiency.
Introduction
  • Clinical definition
    • severe combined immunodeficiency (SCID) is a combined B- and T-cell disorder causing immunodeficiency
      • characterized by recurrent infections
      • multiple variants exist
  • Genetics
    • most common is X-linked defective common gamma chain
      • IL-2R, IL-4R, and IL-7R
      • defective T-cell activation
    • autosomal recessive adenosine deaminase deficiency
      • 2nd most common
      • ↑ deoxyadenosine, which is toxic to lymphocytes
      • ↓ DNA synthesis
    • autosomal recessive JAK-3 deficiency
  • Pathogenesis
    • B-cells
      • decreased immunoglobulin production
    • T-cells
      • markedly decreased T-cells
  • Prognosis
    • without a bone marrow transplant, patients die by 2 years of age
Presentation
  • Symptoms
    • symptoms present before 3 months of age
    • failure to thrive
    • recurrent bacterial, viral, fungal, and protozoal infections
    • chronic diarrhea
  • Physical exam
    • may see thrush in mouth and diaper area
    • eczematous dermatitis
      • erythroderma (> 90% body surface area involvement)
    • severe seborrheic dermatitis
    • diffuse alopecia
    • absent lymphatic tissue, including tonsils and thymus
Studies
  • Diagnostic testing
    • imaging
      • chest radiography
        • no thymic shadow
    • studies
      • normal or ↓ lymphocyte count (< 3,000/μL)
        • however, lymphocyte count may also be normal but dysfunctioning
      • ↓ immunoglobulin levels
      • flow cytometry
        • absent T-cells
        • abnormal function of B-cells
Differential
  • Bruton agammaglobulinemia
    • distinguishing factor
      • similarly presents with recurrent bacterial infections since a young age
      • unlike SCID, there are normal T-cells on flow cytometry
  • DiGeorge syndrome
    • distinguishing factor
      • similarly presents with thymic aplasia and T-cell deficiency
      • unlike SCID, there are normal B-cells, hypoparathyroidism, and associated conotruncal abnormalities
Treatment
  • Management approach
    • mainstay of treatment is to treat each infection that arises
    • bone marrow transplant is the most effective treatment
  • First-line
    • bone marrow transplant
      • indication
        • all patients
Complications
  • Severe infection
  • Death
 

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