Adenosine deaminase deficiency: Frequency and comparative pathology in autosomally recessive severe combined immunodeficiency

Abstract

Seven of thirty families with severe combined immunodeficiency (SCID) had an affected female child, which is presumptive evidence of an autosomal recessive mode of inheritance. Four of these seven families (57%) were found to carry a gene for adenosine deaminase (ADA) deficiency, in that parents and family members had ADA activity in the range of known obligate heterozygotes. In three of the four families, the diagnosis of heterozygosity for ADA deficiency was confirmed either by the subsequent birth of an affected ADA-deficient child or by testing an affected child alive following successful bone marrow transplant. In the fourth family, anomalous inheritance of the ADA genetic polymorphism confirmed the presence of a “null” allele for ADA. Thymic and bony pathology, of a type previously thought to be unique to ADA deficiency, was also found in patients with normal ADA. Retrospective diagnosis of ADA deficiency based solely upon pathologic changes is therefore not reliable.