Neonatal screening for severe combined immunodeficiency. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Basis of Inherited Disease. Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency.

Accessed September 15, 2017.ħ Hershfield MS, Mitchell BS. Department of Health and Human Services, National Institutes of Health, National Library of Medicine, Lister Hill National Center for Biomedical Communications 2016. Immunodeficiency caused by adenosine deaminase deficiency. Accessed August 26, 2017.ĥ Hershfield MS. Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. 2009 114:3524-3532.ģ Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS. 2009 3:349-358.Ģ Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD. Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID). Today, all 50 states, the District of Columbia, and Puerto Rico are currently screening or committed to newborn screening for SCID within the next few years. Babies found to screen positive for SCID can have assays (enzyme tests) and genetic testing for ADA to determine whether they have ADA deficiency before symptoms or illness develop. 7Ī new test known as T-cell Receptor Excision Circles (TREC) can be done at birth to identify babies with SCID and intervene with supportive care. If the mutation leading to SCID in a family is known, an at-risk fetus can be tested using DNA sequencing. SCID can be caused by mutations in at least 15 different genes. The buildup of these biologic products in excess of normal causes the T-cells and B-cells to die, leaving affected individuals with no significant immune defense and increasing their risk of infection. These toxic levels cause specialized lymphocytes called T-cells and B-cells to accumulate biologic chemicals that would normally be processed by ADA. However, mutations in the ADA gene reduce or eliminate the protective activity of adenosine deaminase, allowing the buildup of adenosine and deoxyadenosine to toxic levels. 6ĪDA converts adenosine to inosine and deoxyadenosine to deoxyinosine, molecules that do not harm lymphocytes. When functioning properly, the adenosine deaminase enzyme eliminates molecules called adenosine and deoxyadenosine, which are toxic to lymphocytes. This enzyme is found throughout the body but is most active in lymphocytes, which are specialized white blood cells that protect the body from potentially harmful invaders by making immune proteins called antibodies or by directly attacking infected cells. 6 What Causes ADA-SCID?ĪDA-SCID results from mutations in the ADA gene, which provides instructions for producing the ADA enxyme. 2,5 The disorder is responsible for approximately 15% of SCID cases. 4ĪDA-SCID is estimated to occur in approximately one in 200,000 to one in 1,000,000 newborns around the world. 3 Left untreated, babies with ADA-SCID usually die before they reach age 2 unless they are diagnosed early and effective treatment is started. The average age of diagnosis for patients with ADA-SCID is 4.4 months. Patients with ADA-SCID are also susceptible to recurrent illnesses caused by bacteria, viruses and fungi that often begin within the first few weeks of life.

ADA-SCID is characterized by severe and recurrent opportunistic infections, failure to thrive, profound lymphopenia (reduced number of lymphocytes in the blood) with absent or severely impaired immune function, and metabolic abnormalities. The disorder stems from a deficiency in adenosine deaminase (ADA), an enzyme found throughout the body. Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is a rare, inherited, pediatric disorder that is often fatal when left untreated.

Scid disease