Courtesy of the Bubble Foundation, UK.Ī particular feature is the presence of early-onset severe respiratory symptoms caused by direct toxicity of adenosine metabolites on lung tissue, confirmed in experimental models:- Ada (−/−) mice demonstrate severe pulmonary inflammation, with accompanying accumulation of activated macrophages and eosinophils. Chest radiograph from an infant with adenosine deaminase-deficient severe combined immunodeficiency showing abnormal squaring of the scapulae and cupping deformities at the ends of the ribs. Whilst the infectious complications encountered by patients are the same as for other genetic causes of SCID, the systemic distribution of the enzyme is manifest in non-immunological features, including neurodevelopmental deficits ( Rogers et al., 2001) sensorineural deafness ( Albuquerque and Gaspar, 2004) and skeletal abnormalities, particularly of the scapulae and ribs ( Fig. ADA-deficient SCID is typified by severe pan-lymphocytopenia affecting T- and B-lymphocytes and NK cells. Adenosine deaminase is essential for the irreversible deamination of adenosine to inosine and 2’deoxyadenosine to 2’deoxyinosine and absent or impaired function of ADA causes intracellular and extracellular accumulation of these toxic substrates, and deoxyadenosine triphosphate (dATP). Adenosine deaminase is an indispensible purine salvage pathway enzyme, in which deficiency causes one of the more common autosomal recessive SCID syndromes, accounting for approximately 10–15% of cases in outbred populations ( Gaspar, 2010). Adenosine deaminase (ADA)-deficient SCID, caused by loss of function mutations in the ADA gene, is a systemic metabolic defect.
0 kommentar(er)
