Adenosine Deaminase-Deficient Severe Combined Immunodeficiency and Diffuse Large B-Cell Lymphoma

Adenosine deaminase (ADA) deficiency is an inherited disorder of purine metabolism resulting in severe combined immunodeficiency (SCID). In patients who lack an HLA-identical bone marrow donor, enzyme replacement therapy with polyethylene glycol-conjugated ADA (PEG-ADA) can correct metabolic abnormalities and permit the recovery of protective immune function. An 8-day-old girl born to first cousins was admitted with respiratory distress. Her complete blood count revealed lymphopenia. Her erythrocytes lacked the ADA activity and had markedly elevated total deoxyadenosine nucleotides (dAXP), consistent with ADA deficiency. ADA gene sequence analysis revealed homozygosity (and both parents were heterozygous) for a point mutation in exon 9, c.815G>A, which predicts the nonsense mutation W272X. A matched bone marrow transplant donor could not be found and ADA replacement therapy was initiated. At 3 years of age, the patient was hospitalized with respiratory complaints. Radiological investigations revealed multiple pulmonary nodules and splenic mass. Biopsy findings showed diffuse large B-cell lymphoma. The patient died of infectious complications and intracranial hemorrhage on the 12th day of chemotherapy. Within this case report, we want to emphasize the importance of screening for SCID in newborns with lymphopenia. Second, in our severely affected patient, although ADA replacement therapy corrected metabolic abnormalities and restored sufficient immune function to prevent infections, the T-cell function remained abnormal, which probably contributed to the development of lymphoma.