Orphanet J Rare Dis. 2018 Apr 24;13(1):65. doi: 10.1186/s13023-018-0807-5.

PMID: 29690908

Aisling M Flinn, Andrew R Gennery

Highlights: This article reviews the biology, clinical presentation, diagnosis and treatment of adenosine deaminase (ADA) deficiency.

Abstract

Background: Adenosine deaminase (ADA) deficiency causes an accumulation of toxic purine breakdown by-products, which harm lymphocytes the most, resulting in adenosine deaminase-deficient severe combined immunodeficiency. Other signs include skeletal abnormalities, neurodevelopmental effects, and pulmonary manifestations related with pulmonary-alveolar proteinosis, while lymphocytes are the most affected. Affected children frequently show with persistent infection or pulmonary insufficiency in their early years of life.

Objective: Currently, there are three therapy choices for ADA deficiency. Initial treatment with enzyme replacement therapy may reduce acute symptoms and enable partial immunological reconstitution, but treatment is life-long, immune reconstitution is incomplete, and the reconstituted immune system may nullify the enzyme replacement's effects. Hematopoietic stem cell transplantation has long been the therapy of choice, especially in cases when a matched sibling or well-matched unrelated donor is available. The use of gene addition approaches to correct the genetic defect in autologous haematopoietic stem cell treatment has recently shown immunological and clinical success. The biology, clinical presentation, diagnosis, and treatment of ADA-deficiency are discussed in this article.

Keywords: Adenosine deaminase; Gene therapy; Haematopoietic stem cell transplantation; Neurodevelopment; Pulmonary alveolar proteinosisis; Severe combined immunodeficiency.