title: Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations.
abstract: The authors have reviewed the autopsies of 8 patients with adenosine-deaminase-deficient severe combined immunodeficiency disease (ADA-SCID). Several new findings in nonlymphoid organs, including kidney and adrenal gland, and chondro-osseous tissue indicate the multisystem nature of this disorder. Examination of renal tissue in 7 of 8 cases showed mesangial sclerosis. This was confirmed in 3 cases by electron microscopy. One case, treated with multiple erythrocyte partial exchange transfusions for several years, had no mesangial sclerosis. Six of 8 cases showed adrenal-gland cortical sclerosis. Chondro-osseous tissue from vertebrae and costochondral junctions of 4 cases examined showed typical alterations previously reported in ADA-SCID such as short growth plates with few proliferating and some hypertrophic chondrocytes. The authors report the new observations of necrotic chondrocytes, as well as large amounts of cellular debris. These changes were not observed in the 2 other patients examined, who received bone marrow or multiple partial exchange transfusions. The distribution and severity of these lesions, their relationship to ADA replacement therapy, and their homology to mice treated with a potent ADA inhibitor suggests that, in addition to lymphoid dysfunction, disordered nucleoside metabolism due to absent ADA activity in ADA-SCID may be the cause of diverse multi-system pathologic changes in tissues which continue to differentiate or mature after birth.
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency*; D000302:Adrenal Cortex / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D002356:Cartilage / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000473:pathology*; D007223:Infant; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D009700:Nucleoside Deaminases / Q000172:deficiency*; D010902:Pituitary Gland / Q000473:pathology; D012867:Skin / Q000473:pathology; D013131:Spine / Q000473:pathology
chemical_list: D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase