PMID- 9801258
OWN - NLM
STAT- MEDLINE
DCOM- 19990203
LR  - 20240104
IS  - 0037-1963 (Print)
IS  - 0037-1963 (Linking)
VI  - 35
IP  - 4
DP  - 1998 Oct
TI  - Adenosine deaminase deficiency: clinical expression, molecular basis, and 
      therapy.
PG  - 291-8
AB  - 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.
FAU - Hershfield, M S
AU  - Hershfield MS
AD  - Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
LA  - eng
GR  - DK20902/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Semin Hematol
JT  - Seminars in hematology
JID - 0404514
RN  - EC 3.5.4.4 (Adenosine Deaminase)
SB  - IM
MH  - Adenosine Deaminase/*deficiency/*genetics
MH  - Genetic Therapy
MH  - Humans
MH  - Severe Combined Immunodeficiency/physiopathology/therapy
RF  - 75
EDAT- 1998/11/04 00:00
MHDA- 1998/11/04 00:01
CRDT- 1998/11/04 00:00
PHST- 1998/11/04 00:00 [pubmed]
PHST- 1998/11/04 00:01 [medline]
PHST- 1998/11/04 00:00 [entrez]
PST - ppublish
SO  - Semin Hematol. 1998 Oct;35(4):291-8.