What is the most likely cause of Severe Combined Immunodeficiency (SCID)?

From the Guidelines

Severe Combined Immunodeficiency (SCID) is most likely caused by genetic mutations that affect the development and function of T lymphocytes and often B lymphocytes as well, with adenosine deaminase (ADA) deficiency being one of the specific causes. The condition is characterized by impaired development of functional immune cells, resulting in profound immunodeficiency from birth 1. Some of the key features of SCID include:

• Recurrent severe infections
• Failure to thrive
• Chronic diarrhea
• Profound immunodeficiency from birth The most common form of SCID is X-linked SCID, caused by mutations in the IL2RG gene, but other genetic causes such as ADA deficiency, JAK3 deficiency, RAG1/RAG2 mutations, and IL-7 receptor alpha chain defects can also lead to the condition 1. Without treatment, SCID is typically fatal within the first year of life, but early diagnosis through newborn screening programs has significantly improved outcomes by allowing for intervention before serious infections occur 1. In terms of the provided options, A) Adenosine deaminase deficiency is a correct cause of SCID, while the other options are not directly related to the primary cause of the condition. It's worth noting that SCID can be classified into different types based on the underlying genetic defect, and each type may have distinct clinical features and treatment options 1. Overall, the key to managing SCID is early diagnosis and treatment, which can significantly improve outcomes and quality of life for affected individuals 1.

From the Research

Causes of Severe Combined Immunodeficiency (SCID)

• SCID can be caused by several factors, including genetic mutations that affect the immune system.
• One of the known causes of SCID is Adenosine Deaminase (ADA) deficiency, which is a genetic disorder that affects the production of the ADA enzyme [ 2 ].
• ADA deficiency is responsible for approximately 10-15% of all SCID cases [ 2 , 3 , 4 ].

Relationship between ADA Deficiency and SCID

• ADA deficiency leads to the accumulation of toxic metabolites that impair lymphocyte development and function, resulting in severe combined immunodeficiency [ 4 , 5 ].
• The clinical effects of ADA deficiency are manifest most dramatically in the immune system, where it leads to severe lymphopenia [ 2 ].

Answer to the Question

• Based on the available evidence, the most likely cause of Severe Combined Immunodeficiency (SCID) among the given options is A) Adenosine deaminase deficiency [ 2 , 3 , 4 ].