Severe combined immunodeficiency diagnosis and genetic defects

Immunol Rev. 2024 Mar;322(1):138-147. doi: 10.1111/imr.13310. Epub 2024 Jan 29.

Abstract

Severe combined immunodeficiency (SCID) is a rare and life-threatening genetic disorder that severely impairs the immune system's ability to defend the body against infections. Often referred to as the "bubble boy" disease, SCID gained widespread recognition due to the case of David Vetter, a young boy who lived in a sterile plastic bubble to protect him from germs. SCID is typically present at birth, and it results from genetic mutations that affect the development and function of immune cells, particularly T cells and B cells. These immune cells are essential for identifying and fighting off infections caused by viruses, bacteria, and fungi. In SCID patients, the immune system is virtually non-existent, leaving them highly susceptible to recurrent, severe infections. There are several forms of SCID, with varying degrees of severity, but all share common features. Newborns with SCID often exhibit symptoms such as chronic diarrhea, thrush, skin rashes, and persistent infections that do not respond to standard treatments. Without prompt diagnosis and intervention, SCID can lead to life-threatening complications and a high risk of mortality. There are over 20 possible affected genes. Treatment options for SCID primarily involve immune reconstitution, with the most well-known approach being hematopoietic stem cell transplantation (HSCT). Alternatively, gene therapy is also available for some forms of SCID. Once treated successfully, SCID patients can lead relatively normal lives, but they may still require vigilant infection control measures and lifelong medical follow-up to manage potential complications. In conclusion, severe combined immunodeficiency is a rare but life-threatening genetic disorder that severely compromises the immune system's function, rendering affected individuals highly vulnerable to infections. Early diagnosis and appropriate treatment are fundamental. With this respect, newborn screening is progressively and dramatically improving the prognosis of SCID.

Keywords: SCID; child; diagnosis; genetics; immunodeficiency.

Publication types

  • Review

MeSH terms

  • Agammaglobulinemia*
  • Early Diagnosis
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Infant, Newborn
  • Male
  • Mutation
  • Severe Combined Immunodeficiency* / diagnosis
  • Severe Combined Immunodeficiency* / genetics
  • Severe Combined Immunodeficiency* / therapy
  • T-Lymphocytes

Supplementary concepts

  • Severe combined immunodeficiency due to adenosine deaminase deficiency