Severe Combined Immunodeficiency Disorder (SCID)

Snapshot

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  • A 2-month-old baby boy is brought in for an urgent visit to the pediatrician. He has had several ear infections in his short lifetime and now seems to be struggling with a cold. On physical exam, his tongue is noted to be coated with white film. His scalp and face are covered with a flaky dandruff-like substance. Immediately concerned, his pediatrician orders a chest radiograph, which shows absence of thymic shadow. Flow cytometry is ordered.

Introduction

  • Combined B- and T-cell disorder causing immunodeficiency
  • Life-threatening disease of recurrent infections
  • Pathogenesis
    • multiple variants found
    • most common is X-linked defective common gamma chain
      • found in 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 JAK3 deficiency
    • B-cells
      • decreased immunoglobulin production
    • T-cells
  • markedly decreased T-cells

Presentation

  • Symptoms   
    • symptoms present < 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

Evaluation

  • Diagnosis often delayed due to maternal IgG protecting baby in first few months of life
  • ↓ Lymphocyte count (< 3000/μL)
  • Chest radiography with no thymic shadow
  • Flow cytometry
    • absent T-cells
  • abnormal function of B-cells

Differential Diagnosis

  • Hypogammaglobulinemia
  • DiGeorge syndrome
  • Hyper-IgM syndrome 
  • Ataxia-telangiectasia 

Treatment

  • Bone marrow transplant
    • life-saving treatment
    • no concerns for allograft rejection
  • Gene therapy

Prognosis, Prevention, and Complications

  • Prognosis
    • without intervention, death by 2 years
    • patients < 6 months of age who receive transplant have the best outcomes
  • Complications
    • severe infection
    • death