Abstract

Adenosine deaminase deficiency (ADA) is an autosomal recessive disorder of purine metabolism that leads to the accumulation of toxic metabolites that impairs lymphocyte differentiation, viability, and function, resulting in severe combined immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase minimises infectious complications of patients who lack an HLA-identical bone marrow donor.

An 8-day-old girl was admitted to our hospital with respiratory distress. The patient’s parents were first degree cousins. Her complete blood count revealed lymphopaenia with the following differentiation: CD3 T cell: 0.9%; CD19 B cell: 0.9%; CD4: 0%; CD8: 0%; natural killer cell: 4.3%. ADA activity was markedly deficient. Metabolic findings were consistent with ADA deficiency, including elevated deoxyadenosine nucleotide. Mutation analyses revealed a novel nonsense mutation of codon 272 (W272X). Our patient was homozygous and both parents were heterozygous for this mutation. A matched bone marrow transplant donor could not be found and ADA-replacement therapy was initiated. At the second week of PEG-ADA treatment total lymphocyte count increased to 1327/mm³ and B lymphocyte and natural killer cell counts reached normal values. Total deoxyadenosine nucleotides (dAXP) in red blood cells declined to normal range and plasma ADA enzyme activity increased. During 16 months follow-up on PEG-ADA treatment the patient was excellent without any severe infection.

This report emphasises the importance of screening for severe combined immunodeficiency in newborns with lymphopaenia and the efficacy of enzyme replacement therapy for ADA-deficient severe combined immunodeficient patients who lack HLA matched donors.