How I treat ADA deficiency.

@article{Gaspar2009HowIT,
  title={How I treat ADA deficiency.},
  author={H Bobby Gaspar and Alessandro Aiuti and Fulvio Porta and Fabio Candotti and Michael S. Hershfield and Luigi Daniele Notarangelo},
  journal={Blood},
  year={2009},
  volume={114 17},
  pages={
          3524-32
        }
}
Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous… 
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207 Citations

How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID)

This work proposes a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HS CT from an unrelated or haplo-identical donor or long-term ERT as other options.

Adenosine deaminase deficiency: current treatments and emerging therapeutics

GT should be considered for patients without an appropriate HSCT donor and when families are able to travel to Italy or participate in research protocols, although long-term follow up is needed to determine their continued effectiveness.

Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.

Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency.

This investigation investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT.

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency

The value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms and the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency are assessed.

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

It is demonstrated 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 and thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition.

National experience with adenosine deaminase deficiency related SCID in Polish children

It is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs, and implementation of Newborn Screening for SCID in Poland could enable recognition of SCID, including ADA-SCID.

Severe Combined Immunodeficiencies Resulting from Impaired Purine Metabolism: Single Center Experience

It was highlighted once again that the deficiency of purine salvage enzymes is important subgroup of SCIDs in Turkey.

MANAGEMENT OF ADENOSINE DEAMINASE DEFICIENCY: A REVIEW ARTICLE

The aim of this paper is to present an overview of ADA deficiency and the available treatment modalities and to suggest antibiotic prophylaxis specific treatment provided based on individualized level.

A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient

A 24-year course of treatment in a patient who was diagnosed with ADA deficiency has resulted in near-normalization of lymphocyte counts, and this patient is among the longest to be maintained on PEG-ADA enzyme replacement therapy.
...

References

SHOWING 1-10 OF 52 REFERENCES

Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006).

Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.

The high rate of neurologic abnormalities observed in long-term surviving patients with ADA deficiency indicates that HSCT commonly fails to control CNS complications in this metabolic disease.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency and effective protection against infections and improvement in physical development made a normal lifestyle possible.

Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).

Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol‐adenosine deaminase‐treated patients

Data indicate that decreased thymic function, B cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by which the immunodeficiency of ADA‐SCID patients persists in spite of treatment with PEG‐ADA.

Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.

Cerebral Lymphoma in an Adenosine Deaminase–Deficient Patient With Severe Combined Immunodeficiency Receiving Polyethylene Glycol–Conjugated Adenosine Deaminase

A 10-year-old child who was diagnosed with ADA-severe combined immunodeficiency at 4 weeks of age after contracting pneumonia is presented and it is speculated that the immunologic surveillance by T cells may have been defective with respect to elimination of Epstein-Barr virus–infected cells, hence the formation of neoplasm.

Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning

Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions, and lower toxic metabolites, indicating the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.

Severe combined immunodeficiency. A model disease for molecular immunology and therapy

Based on the assumption that long‐lasting pluripotent progenitor cells are transduced, these data suggest that gene therapy could overcome the long‐term recurrence of the T‐cell immunodeficiency.

Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.
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