Clinical Guidance

Adenosine deaminase (ADA) deficiency (also referred to as adenosine deaminase 1 deficiency, or ADA1 deficiency) is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function [, , , ]. ADA is expressed in all cells, but is most highly expressed in lymphocytes; thus, in some individuals, ADA deficiency can affect non-lymphoid organs such as the lungs, liver, kidneys, and nervous system (resulting in behavioral abnormalities) . The phenotypic spectrum of ADA deficiency includes typical early-onset severe combined immunodeficiency (ADA-SCID), diagnosed in infancy (about 80% of individuals), and less severe "delayed" or "late-onset" combined immunodeficiency (ADA-CID), diagnosed in older children and adults (15%-20% of individuals).

Diagnostic Criteria

Adenosine deaminase (ADA) deficiency cannot be diagnosed solely on clinical grounds. The Primary Immune Deficiency Treatment Consortium (PIDTC) has established laboratory-based definitions for severe combined immunodeficiency (SCID) .

Suggestive Findings

The two scenarios in which ADA deficiency may be considered are a and a of any age with suggestive clinical and laboratory findings of combined immunodeficiency (CID). In both scenarios, individuals identified warrant immediate subspecialty immunology evaluation and steps taken to ensure the safety of a baby or older individual pending establishment of the diagnosis and treatment.

Management Guidelines

Consensus recommendations for managing severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency have been published . These guidelines focus on correction of the ADA deficiency and the restoration of immune function. No recommendations or guidelines have been developed for the management of systemic (non-immunologic) abnormalities associated with ADA deficiency, which varies among medical centers and practitioners.

Surveillance Guidelines

Response to targeted therapy. To monitor the individual's response to targeted treatment, the following evaluations are recommended.

• Immune function. Frequent evaluation of lymphocyte counts, serum immunoglobulin levels, and various in vitro tests of cellular and humoral immune function should be performed during ERT and following allogenic HSCT and HSC-GT .