ADULT-ONSET IMMUNODEFICIENCY CAUSED BY INHERITED ADENOSINE-DEAMINASE DEFICIENCY

Adenosine deaminase (ADA) deficiency is identified here as a cause of adult onset immunodeficiency. Two sisters who noted recurrent, predomi nantly chest infections in their twenties were found in their thirties to have CD4(+) lymphopenia and lymphocyte ADA activity of approximate ly 5% of the lower limit of normal. Immune function, measured by proli feration of PBMCs in vitro to mitogens and specific Ags, was impaired. Inheritance of a polymorphic marker showed that both patients were he terozygous at the ADA locus. In the paternal allele there was a deleti on resulting from homologous recombination between two alu elements th at normally flank the first exon and the polymorphic marker. The recom bination site was distinct from that in similar deletions described in two infants having severe combined immunodeficiency. This allele is p redicted to result in a null phenotype. In the mutant allele inherited from the mother, a C to T transition in a CpG dinucleotide changed th e codon for arginine 211, which lies in a conserved sequence close to the active site, to that for cysteine. This mutation has been observed previously in a child in whom the other allele was also a null mutati on, but who was diagnosed as having partial ADA deficiency because imm une function was apparently normal. The late onset of immunodeficiency in our patients suggests that immune function in children with partia l ADA deficiency may deteriorate with time and that ADA deficiency sho uld be regarded as a possible cause of adult onset immune dysfunction of unknown etiology.