Severe combined immunodeficiency due to adenosine deaminase deficiency

Inherited ADA deficiency resulting in immunodeficiency. It accounts for 15 % of SCID cases in infancy. Partial ADA deficiency may occur in some immunocompetent patients, who show decreased enzyme activity in erythrocytes, but retain sufficient enzyme activity in leukocytes and other nucleated cells. OMIM: 102700

Also Known As:

ADA Deficiency; ADA-SCID; Adenosine Deaminase Deficiency, Partial; Adenosine Deaminase Deficient Severe Combined Immunodeficiency; Adenosine deaminase deficiency; Adenosine deaminase-deficient severe combined immunodeficiency disease; Agammaglobulinemia, Swiss type; Bubble boy disease; Delayed-Late-Onset Adenosine Deaminase Deficiency; Partial ADA Deficiency; Partial adenosine deaminase deficiency; SCID Due to ADA Deficiency; SCID Due to ADA Deficiency, Delayed Onset; SCID Due to ADA Deficiency, Early-Onset; SCID Due to ADA Deficiency, Late-Onset; SCID1; Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Negative, Due To Adenosine Deaminase Deficiency; Severe combined immunodeficiency, alymphocytotic type

Networked: 502 relevant articles (24 outcomes, 41 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Severe Combined Immunodeficiency (Bare Lymphocyte Syndrome)
2.	X-Linked Combined Immunodeficiency Diseases (X Linked Severe Combined Immunodeficiency)
3.	Wiskott-Aldrich Syndrome
4.	Chronic Granulomatous Disease
5.	Acquired Immunodeficiency Syndrome (AIDS)

Experts

1.	Aiuti, Alessandro: 37 articles (01/2021 - 05/2002)
2.	Hershfield, Michael S: 22 articles (01/2022 - 02/2002)
3.	Gaspar, H Bobby: 19 articles (01/2022 - 09/2005)
4.	Kohn, Donald B: 15 articles (01/2022 - 01/2003)
5.	Roncarolo, Maria Grazia: 13 articles (01/2018 - 05/2002)
6.	Candotti, Fabio: 12 articles (10/2021 - 02/2002)
7.	Ferrua, Francesca: 12 articles (01/2021 - 01/2009)
8.	Grunebaum, Eyal: 10 articles (01/2021 - 07/2007)
9.	Brigida, Immacolata: 10 articles (01/2016 - 01/2009)
10.	Carlucci, Filippo: 9 articles (11/2017 - 05/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Severe combined immunodeficiency due to adenosine deaminase deficiency:

1.	Adenosine DeaminaseIBA 11/01/2011 - "Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. " 08/15/1999 - "In vivo kinetics of transduced cells in peripheral T cell-directed gene therapy: role of CD8+ cells in improved immunological function in an adenosine deaminase (ADA)-SCID patient." 11/01/1993 - "We examined the genetic basis for adenosine deaminase (ADA) deficiency in seven patients with late/delayed onset of immunodeficiency, an underdiagnosed and relatively unstudied condition. " 02/01/2009 - "We report detailed genetic and immunologic studies in a patient diagnosed with adenosine deaminase (ADA) deficiency and combined immune deficiency at age 5 years. " 02/10/2002 - "Clinical gene therapy trials for adenosine deaminase (ADA) deficiency have shown limited success of corrective gene transfer into autologous T lymphocytes and CD34(+) cells. "
2.	purineIBA 12/01/2009 - " trials represented the first demonstration of long-term clinical efficacy of HSC gene therapy for ADA-SCID, underlining that gene therapy has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions. " 01/01/2009 - "Recent studies have demonstrated that gene therapy for ADA-SCID has favorable safety profile and is effective in restoring normal purine metabolism and immune functions. " 01/01/2022 - "Adenosine deaminase deficiency (ADA) is a purine salvage pathway deficiency that results in buildup of toxic metabolites causing death in rapidly dividing cells, especially lymphocytes. " 02/09/2012 - "Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. " 01/01/2012 - "Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency."
3.	pegademase bovine (pegADA)FDA Link 12/01/2021 - "Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. " 12/01/2021 - "Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. " 01/01/2020 - "Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. " 01/01/2009 - "We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options." 10/01/2006 - "Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning."
4.	elapegademaseIBA 01/01/2023 - "REVCOVI is effective for the management of ADA-SCID." 01/01/2023 - "Safety and efficacy of elapegademase in patients with adenosine deaminase deficiency: A multicenter, open-label, single-arm, phase 3, and postmarketing clinical study." 01/01/2023 - "REVCOVI treatment in the ERT-naive group led to the resolution of many clinical and laboratory complications of ADA deficiency, whereas there were no new adverse effects among the transitioning patients. " 01/01/2023 - "Data on ERT, infectious and noninfectious complications, and metabolic and immune evaluations were collected from 17 patients with ADA-SCID treated for 6 months or more with REVCOVI. " 01/01/2023 - "To determine the real-life long-term benefits of REVCOVI in ADA-SCID. "
5.	EnzymesIBA 12/01/2021 - "Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency." 08/01/2011 - "In this study, recombinant adeno-associated virus (rAAV) vectors based on serotypes 1 and 9 were used to deliver a secretory version of the human ADA (hADA) gene to various tissues to promote immune reconstitution following enzyme expression in a mouse model of ADA deficiency. " 01/01/2024 - "Other mutations that reduce enzyme activity, for instance the Asp8Asn (D8N) variant, do not cause ADA-SCID but are correlated with other consequences to health. " 09/01/2021 - "Enzyme ADA deficiency represents from 10% to 15% of the SCID. " 01/01/2018 - "Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. "
6.	DeoxycytidineIBA 10/01/1985 - "This study defines some of the pharmacologic parameters of human deoxycytidine metabolism and suggests that some patients with ADA deficiency may respond to deoxycytidine therapy with improvement in T-cell-mediated immunity, although the changes are small and the effect on clinical status appears to be limited." 10/01/1985 - "Deoxycytidine therapy in two patients with adenosine deaminase deficiency and severe immunodeficiency disease." 01/01/1984 - "Intravenous deoxycytidine therapy in a patient with adenosine deaminase deficiency." 10/01/1985 - "Two children with adenosine deaminase (ADA) deficiency and combined immunodeficiency disease were given parenteral deoxycytidine in order to reverse the severe T-cell immunodeficiency associated with this disease. " 11/01/1982 - "Effect of red cell transfusions, thymic hormone and deoxycytidine in severe combined immunodeficiency due to adenosine deaminase deficiency."
7.	Adenosine Triphosphate (ATP)IBA 10/01/1984 - "dATP accumulation and ATP depletion in platelets in adenosine deaminase deficiency: significance for the immune response?" 12/01/1983 - "This reciprocal relationship between ATP and dATP was found by us previously in the erythrocytes in inherited ADA deficiency. " 08/15/2000 - "Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. " 10/01/1985 - "They cast doubt on the validity of cultured cells as a model for ADA deficiency and suggest the observed toxicity in some instances might result from altered ATP or GTP pools through inadequate ADA inhibition. " 01/01/1985 - "Abnormalities in S-adenosylhomocysteine hydrolysis, ATP catabolism, and lymphoid differentiation in adenosine deaminase deficiency."
8.	CD40 Ligand (CD40L)IBA 08/15/2000 - "Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. " 12/01/2022 - "All patients went gene sequencing and were finally diagnosed as IEIs, including STAT1 gain-of-function, IL-2 receptor common gamma chain deficiency, adenosine deaminase deficiency, CD40 ligand deficiency, and STAT3 deficiency. " 05/01/1999 - "We also examined the expression of IL-4 and CD40 ligand by CD8(+) T cells from a patient with adenosine deaminase deficiency who received autologous T cell-directed gene therapy. "
9.	Lithium ChlorideIBA 09/23/1982 - "Lithium chloride, a potent inhibitor of adenylate cyclase, not only improved lymphocyte activity in a patient with adenosine deaminase deficiency but also enhanced the phytohaemagglutinin (PHA)-induced responses of normal human lymphocytes. "
10.	Interleukin-7 (Interleukin 7)IBA 12/01/2004 - "Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. " 12/01/2004 - "IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential." 12/01/2004 - "Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34(+) cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. "

Therapies and Procedures

1.	Therapeutics 10/01/2007 - "Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective." 03/01/2020 - "This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X, ADA-SCID, WAS, X- CGD, and the recent developments in genome editing technology applied in HSCs for developing potential therapy, particular in the key studies for PIDs." 01/01/2018 - "Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). " 01/01/2018 - "There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. " 01/01/2017 - "Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products."
2.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 08/01/1993 - "ADA-SCID patients can be cured by HLA-matched sibling donor bone marrow transplantation. " 02/01/2013 - "Successful bone marrow transplantation with reduced intensity conditioning in a patient with delayed-onset adenosine deaminase deficiency." 10/01/2010 - "Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID." 05/01/2010 - "Bone marrow transplantation and alternatives for adenosine deaminase deficiency." 12/01/2009 - "Recent reports show that ADA-SCID is associated with an increased frequency of autoimmune manifestations and high risk of central nervous system (CNS) complications even after bone marrow transplantation. "
3.	Aftercare (After-Treatment) 01/01/2012 - "Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. " 11/01/2017 - "Recent clinical trials demonstrated that gamma-retroviral GT for ADA-SCID has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions in patients >13 years after treatment. " 06/01/2012 - "However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. "
4.	Enzyme Replacement Therapy 10/01/1978 - "In contrast to a previous report of successful therapy of ADA deficiency with red cell and plasma infusions, this patient responded poorly to enzyme replacement therapy. " 06/24/2023 - "We recommend the prompt initiation of enzyme replacement therapy and secondary prophylaxis to reduce the risk of BCG-related complications in ADA-SCID patients." 01/01/2022 - "Treatment with enzyme replacement therapy (ERT) was developed in the 1970s and became the treatment for ADA SCID by the 1980s. " 12/15/2021 - "Author Correction: Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy." 12/01/2021 - "While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). "
5.	Enzyme Therapy 10/13/2000 - "This model will be useful in examining the efficacy of ADA enzyme therapy and studying the mechanisms underlying the immunodeficiency and pulmonary phenotypes associated with ADA deficiency." 10/13/2000 - "The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. " 03/20/2003 - "Polyethylene glycol-conjugated adenosine phosphorylase: development of alternative enzyme therapy for adenosine deaminase deficiency."