The best-known form of autosomal recessive SCID is caused by adenosine deaminase (ADA) deficiency, in which infants lack the ADA enzyme necessary for T-cell survival. Most often, SCID is inherited in an autosomal recessive pattern, in which both copies of a particular gene-one inherited from the mother and one from the father-contain defects. More than a dozen genes have been implicated in SCID, but gene defects are unknown in approximately 15 percent of newborn-screened SCID infants, according to an NIH-funded study. However, development of a newborn screening test has made it possible to detect SCID before symptoms appear, helping ensure that affected infants receive life-saving treatments. More than 80 percent of SCID infants do not have a family history of the condition. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy, or enzyme therapy. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.ĪDA enzyme replacement therapy Late-onset adenosine deaminase deficiency SCID.Severe combined immunodeficiency (SCID) is a group of rare disorders caused by mutations in different genes involved in the development and function of infection-fighting immune cells. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. The genetic diagnosis of SCID is utmost important. HSCGT was performed to one of the patients. Four out of six patients were transplanted without using a conditioning regimen. Nine out of 13 patients were put on pegylated ADA ERT. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. Seven out of 11 patients with SCID had homozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Four out of 11 patients had compound heterozygous defects.

Genetic defect was documented in 11 patients. All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9).

Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency.

What does ada scid stand for