Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy.

Published

Journal Article (Review)

Adenosine deaminase (ADA) deficiency is the first known cause of severe combined immunodeficiency disease (SCID). Over the past 25 years, the metabolic basis for immune deficiency has largely been established. The clinical spectrum associated with ADA deficiency is now quite broad, including older children and adults. The ADA gene has been sequenced, the structure of the enzyme has been determined, and over 50 ADA gene mutations have been identified. There appears to be a quantitative relationship between residual ADA activity, determined by genotype, and both metabolic and clinical phenotype. ADA deficiency has become a focus for novel approaches to enzyme replacement and gene therapy. Enzyme replacement with polyethylene glycol (PEG)-modified ADA, used to treat patients who lack a human leukocyte antigen (HLA)-matched bone marrow donor, is safe and effective, but expensive. Several approaches to gene therapy have been investigated in patients receiving PEG-ADA. Persistent expression of transduced ADA cDNA in T lymphocytes and myeloid cells has occurred in a few patients, but significant improvement in immune function because of the transduced cells has not been shown. The major barrier to effective gene therapy remains the low efficiency of stem cell transduction with retroviral vectors.

Full Text

Duke Authors

Cited Authors

  • Hershfield, MS

Published Date

  • October 1998

Published In

Volume / Issue

  • 35 / 4

Start / End Page

  • 291 - 298

PubMed ID

  • 9801258

Pubmed Central ID

  • 9801258

International Standard Serial Number (ISSN)

  • 0037-1963

Language

  • eng

Conference Location

  • United States