Adenosine Deaminase Deficiency (ADA)
Adenosine deaminase deficiency is a pan-ethnic, autosomal recessive disease caused by pathogenic variants in the ADA gene. Because this disorder affects lymphocyte function, evidence of severe combined immunodeficiency disease is noted within the first year of life. Other indications of immune failure include depletion of lymphocytes, frequent infections, and pulmonary insufficiency. Infants exhibit failure to thrive, growth failure, chronic diarrhea, and absence of tonsils and lymph nodes. If compromised immunity cannot be restored, life expectancy is predicted to be between one to two years. However, clinically variable phenotypes have also been noted. Delayed onset of the disease in childhood results in a milder form in approximately 15-20% of individuals, characterized by recurring infections, allergies, and persistent warts. A benign form of the condition, called partial adenosine deaminase deficiency, results if residual ADA activity remains in nucleated cells. Individuals with this form of the disease have normal immune function. ADA-deficient severe combined immune deficiency results when both alleles carry a null variant, whereas the later-onset form of the disease results from the presence of at least one missense variant that results in significantly decreased, but not eliminated, ADA activity. Partial ADA deficiency is seen when at least one of the two pathogenic variants exhibits only slightly decreased ADA activity.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.