Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency

J Clin Immunol. 2012 Jun;32(3):449-53. doi: 10.1007/s10875-012-9658-3. Epub 2012 Feb 21.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Deaminase / deficiency
  • Adenosine Deaminase / therapeutic use
  • Agammaglobulinemia / diagnosis*
  • Agammaglobulinemia / microbiology
  • Agammaglobulinemia / therapy
  • Bronchoalveolar Lavage
  • Child, Preschool
  • Enzyme Replacement Therapy
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Infant, Newborn
  • Lung Diseases / diagnosis*
  • Lung Diseases / microbiology
  • Lung Diseases / therapy
  • Male
  • Severe Combined Immunodeficiency / diagnosis*
  • Severe Combined Immunodeficiency / microbiology
  • Severe Combined Immunodeficiency / therapy
  • Tomography, X-Ray Computed
  • X-Linked Combined Immunodeficiency Diseases / diagnosis*
  • X-Linked Combined Immunodeficiency Diseases / microbiology
  • X-Linked Combined Immunodeficiency Diseases / therapy

Substances

  • Adenosine Deaminase

Supplementary concepts

  • Severe combined immunodeficiency due to adenosine deaminase deficiency