Adenosine Deaminase (ADA) Deficiency: A Functional in Vitro Assay to Assess the Pathogenicity Potential of 44 Novel ADA Gene Variants of Unknown Significance (VUS).

Asymptomatic ADA deficient infants may be identified by neonatal TREC or mass spectrometry screens. However, many carry VUS, and absent RBC ADA activity does not distinguish patients with severe combined immunodeficiency (SCID), a delayed/late onset phenotype, or benign "partial ADA deficiency". In 1998, we reported that ADA activity expressed by 29 ADA missense variants in an ADA-strain of E. coli correlated with phenotype and level of RBC deoxyadenosine nucleotides (dAXP), a marker of systemic ADA function1.