Severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a group of inherited genetic disorders characterised by a profound deficiency in cellular and humoral immunity arising from one of many T-cell maturation defects in the bone marrow or thymus gland.

Infants with SCID usually appear healthy at birth. Over time, they may develop: recurrent or severe infections; increased susceptibility to opportunistic infections; faltering growth; and/or chronic diarrhoea.

Newborn screening for T-cell deficiency can alert for SCID before infections and other signs of SCID develop.

Early diagnosis is imperative as, without curative treatment (e.g., haematopoietic stem cell transplantation, gene therapy, enzyme replacement therapy), the condition can be fatal in the first year of life.

Key findings on examination include the absence of lymphoid tissue, poor weight gain, or diffuse erythematous rash. Other factors alerting for SCID include absolute lymphopenia and absent thymus.

Antibacterial, antifungal, and antiviral prophylaxis should be considered for patients with suspected or confirmed SCID.

Live vaccines (e.g., BCG, rotavirus, and oral polio) should not be given to infants with suspected or diagnosed SCID. Cytomegalovirus (CMV) infection by breastfeeding should be prevented when possible.

Blood or blood products should be irradiated, leukocyte depleted, and negative for CMV before being administered to patients with confirmed or suspected SCID.

Severe combined immunodeficiency (SCID) is a group of inherited genetic disorders characterised by a severe deficiency of adaptive cellular and humoral immunity arising from one of many T-cell maturation defects in the bone marrow or thymus gland.[1]Rivers L, Gaspar HB. Severe combined immunodeficiency: recent developments and guidance on clinical management. Arch Dis Child. 2015 Jul;100(7):667-72. http://www.ncbi.nlm.nih.gov/pubmed/25564533?tool=bestpractice.com

T cells are absent in most forms of SCID; the absence and presence of B cells and natural killer cells varies depending on the type of SCID.[2]Bousfiha A, Moundir A, Tangye SG, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. J Clin Immunol. 2022 Oct 6 [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/36198931?tool=bestpractice.com [3]Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 Jun 24;1-35 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244088 http://www.ncbi.nlm.nih.gov/pubmed/35748970?tool=bestpractice.com

Clinical manifestations begin early in life and include: severe and recurrent infections; increased susceptibility to opportunistic infections; faltering growth; and/or chronic diarrhoea.[4]Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205.e1-78. http://www.jacionline.org/article/S0091-6749(15)00883-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/26371839?tool=bestpractice.com [5]Routes J, Abinun M, Al-Herz W, et al. ICON: The early diagnosis of congenital immunodeficiencies. J Clin Immunol. 2014 May;34(4):398-424. http://www.ncbi.nlm.nih.gov/pubmed/24619621?tool=bestpractice.com