Severe combined immunodeficiency

Author: Brian Wu PhD. MD Candidate, Keck School of Medicine, Los Angeles, USA; Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, October 2015.


What is severe combined immunodeficiency?

Severe combined immunodeficiency (SCID) is considered to be the most serious of all primary immunodeficiencies. This rare congenital disorder is potentially fatal, due to severely compromised immune system marked by a combined absence of T-lymphocyte and B-lymphocyte function.

What causes severe combined immunodeficiency?

There are at least 13 different genetic defects associated with severe combined immunodeficiency. These defects interfere with the formation of lymphocytes. Around 70% of those with SCID are able to produce B-cells, but around 30% do not. In certain forms of this condition, the production of natural killer cells is also affected.

What are the risk factors for severe combined immunodeficiency?

There are risk factors of age, sex and ethnicity:

  • Age. Most patients with SCID present by age 3 months.
  • Sex. The most common form of SCID (responsible for about 45% of all cases) is X-linked and only presents in males. Other forms, however, can present in males and females equally.
  • Ethnicity. Certain ethnic groups — including the Finnish, North Africans, Italians, Navajos and Apaches — appear to carry a greater risk for specific forms of this condition.

What are the signs and symptoms of immunodeficiency?

The signs and symptoms of immunodeficiency in SCID can vary, but do include:

  • History of severe and/or recurrent infections, which can include meningitis, pneumonia, bloodstream infections and viral infections from varicella, cytomegalovirus, herpes simplex, adenovirus, parainfluenza, Epstein-Barr, poliovirus, measles or the rotavirus. Candida fungal infections are common. Protozoal infections that cause severe diarrhoea are possible
  • Neurological impairments, including cognitive, auditory and visual impairments
  • Musculoskeletal issues such as muscle weakness and/or low muscle tone
  • Dermatological problems including eczematous dermatitis, granulomas with a predominance of CD8+ cells, dermatofibrosarcoma protuberans (in SCID associated with adenosine deaminase (ADA) deficiency)
  • Adverse reaction to vaccines such as BCG

How is severe combined immunodeficiency diagnosed?

The diagnosis severe combined immunodeficiency can be made from:

  • Presenting signs and symptoms
  • Known family history of the disease
  • Complete blood count (CBC) plus a manual differential to calculate the absolute lymphocyte count
  • T-cell function tests
  • In utero prenatal genetic testing via chorionic villous sampling (CVS) or amniocentesis
  • Neonatal screening

How is severe combined immunodeficiency treated?

The gold standard for SCID is a stem cell reconstitution from bone marrow transplant in the first 3 months of life, a procedure which has a 94% success rate. Immunoglobulin therapy is also common, as is gene therapy for X-linked ADA deficiency. ADA deficiency is sometimes also treated with injections of a modified form of ADA (an enzyme).

Treatment is critical. Without intervention, death will general occur by age 2.

 

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