title: Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency.
abstract: Adenosine deaminase deficiency is a disorder of purine metabolism manifesting severe combined immunodeficiency (ADA-SCID) and systemic abnormalities. Increased levels of the substrate deoxyadenosine triphosphate (dATP) lead to immunodeficiency and are associated in a murine model with pulmonary insufficiency. We compared a cohort of patients with ADA-SCID and X-linked SCID and found that despite similar radiological and respiratory findings, positive microbiology is significantly less frequent in ADA-SCID patients (p < 0.0005), suggesting a metabolic pathogenesis for the lung disease. Clinicians should be aware of this possibility and correct metabolic abnormalities either through enzyme replacement or haematopoietic stem cell transplant, in addition to treating infectious complications.
authors.affiliation: Centre of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: C
authors.initials: C
authors.lastname: Booth
authors.forename: V E
authors.initials: VE
authors.lastname: Algar
authors.forename: J
authors.initials: J
authors.lastname: Xu-Bayford
authors.forename: L
authors.initials: L
authors.lastname: Fairbanks
authors.forename: C
authors.initials: C
authors.lastname: Owens
authors.forename: H B
authors.initials: HB
authors.lastname: Gaspar
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency / Q000627:therapeutic use; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy; D018893:Bronchoalveolar Lavage; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008171:Lung Diseases / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy; D014057:Tomography, X-Ray Computed; D053632:X-Linked Combined Immunodeficiency Diseases / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy
chemical_list: D000243:Adenosine Deaminase