Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants.
OBJECTIVE
To determine the relative frequencies of the different genetic forms of severe combined immunodeficiency (SCID) and whether there are distinctive characteristics of the particular genotypes.


METHODS
The demographic, genetic, and immunologic features of 108 infants with SCID who were treated consecutively at Duke University Medical Center were analyzed.


RESULTS
Eighty-nine subjects were boys and 19 were girls; there were 84 white infants, 16 black infants, and 8 Hispanic infants. Forty-nine had X-linked SCID with mutations of common cytokine receptor gamma chain (gamma c), 16 had adenosine deaminase (ADA) deficiency, 8 had Janus kinase 3 (Jak3) deficiency, 21 had unknown autosomal recessive mutations, 1 had reticular dysgenesis, 1 had cartilage hair hypoplasia, and 12 (all boys) had SCID of undetermined type. Deficiency of ADA caused the most profound lymphopenia; gamma c or Jak3 deficiency resulted in the most B cells and fewest natural killer (NK) cells; NK cells and function were highest in autosomal recessive and unknown types of SCID.


CONCLUSIONS
Different SCID genotypes are associated with distinctive lymphocyte characteristics. The presence of NK function in ADA-deficient, autosomal recessive, and unknown type SCIDs, and low NK function in a majority of gamma c and Jak3 SCIDs indicates that some molecular lesions affect T, B, and NK cells (gamma c and Jak3), others primarily T cells (ADA deficiency), and others just T and B cells.
Buckley
R H
RH
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schiff
R I
RI
Schiff
S E
SE
Markert
M L
ML
Williams
L W
LW
Harville
T O
TO
Roberts
J L
JL
Puck
J M
JM
D000243:Adenosine Deaminase / Q000172:deficiency; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D053616:Janus Kinase 3; D008297:Male; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D014960:X Chromosome
D007136:Immunoglobulins; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D000243:Adenosine Deaminase