Neonatal screening for severe combined immunodeficiency caused by an adenosine deaminase defect: A reliable and inexpensive method using tandem mass spectrometry

• Published in: Journal of allergy and clinical immunology Vol. 127; no. 6; pp. 1394 - 1399
• Main Authors: Azzari, Chiara, la Marca, Giancarlo, Resti, Massimo
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.06.2011; Elsevier; Elsevier Limited
• Subjects: adenosine; Adenosine - blood; Adenosine deaminase; Adenosine Deaminase - blood; Adenosine Deaminase - deficiency; Agammaglobulinemia - blood; Agammaglobulinemia - diagnosis; Allergy and Immunology; Amino acids; Biological and medical sciences; blood; Blood Chemical Analysis - economics; Blood Chemical Analysis - methods; Blood Chemical Analysis - statistics & numerical data; bone marrow transplant; Case-Control Studies; Child; Child, Preschool; children; Costs and Cost Analysis; Defects; Deoxyadenosines - blood; Enzymes; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gene therapy; Humans; Immune system; Immunopathology; immunosuppression; infancy; Infant; Infant, Newborn; Infections; Italy; Laboratories; Male; Mass spectrometry; Medical sciences; Medical screening; Metabolism; Metabolites; Methods; Neonatal Screening - economics; Neonatal Screening - methods; neonates; Newborn babies; newborn screening; patients; Pilot Projects; Reproducibility of Results; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; screening; Sensitivity and Specificity; severe combined immunodeficiency; Severe Combined Immunodeficiency - blood; Severe Combined Immunodeficiency - diagnosis; tandem mass spectrometry; Tandem Mass Spectrometry - economics; Tandem Mass Spectrometry - methods; Tandem Mass Spectrometry - statistics & numerical data; Urine; Italy; tandem mass spectrometry; DBS; Adenosine deaminase; TREC; severe combined immunodeficiency; newborn screening; SCID; ADA; Dried blood spot; T-cell receptor gene excision circle; Human; Immunopathology; Neonatal; Severe combined immunodeficiency; Enzyme; Exploration; Method; Medical screening; Immunology; Newborn; Hydrolases; Combined immune deficiency; Mass spectrometry
• ISSN: 0091-6749; 1097-6825; 1085-8725; 1097-6825
• DOI: 10.1016/j.jaci.2011.03.040

Adenosine deaminase (ADA)–severe combined immunodeficiency (SCID) is an SCID caused by a defect in the enzyme adenosine deaminase. It is usually fatal in infancy because of severe recurrent infections. When diagnosis is made, permanent damage caused by infections or by metabolites is often present. Gene therapy, bone marrow transplantation, or enzyme therapy might be effective if performed early. ADA-SCID complies with all the criteria for inclusion in a newborn screening program. However, screening methods are still expensive or provide a non-negligible number of indeterminate results. The aim of the present study was to develop a simple, reliable, and inexpensive method for diagnosis of ADA-SCID by using dried blood spot (DBS) samples taken at birth. Cost per test was calculated, including the cost for reagents, equipment, and operators. DBS samples from 4 patients with genetically confirmed ADA-SCID and 12,020 DBS samples from healthy newborns were examined. Adenosine and 2′-deoxyadenosine were tested by using tandem mass spectrometry (PCT EP2010/070517). The mean levels of adenosine and 2′-deoxyadenosine were 7.8 ± 3.1 and 8.5 ± 6.0 μmol/L, respectively, in affected children; adenosine was found at 0.23 ± 0.09 μmol/L, whereas 2′-deoxyadenosine was never detected in healthy control subjects (adenosine: P < 10 −6 [95% confidence limit, 7.59-7.78] and 2′-deoxyadenosine: P < 10 −6 [95% confidence limit, 8.65-8.82] for control subjects vs patients with ADA-SCID). No indeterminate or false-positive results were found. Cost per test was €0.01 ($0.013). A pilot population-based newborn screening for ADA-SCID has started in Tuscany, Italy. Tandem mass spectrometry can be used for diagnosis of one of the most frequent form of SCID at a negligible cost.