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Severe Combined Immunodeficiency due to Adenosine Deaminase Deficiency

ADA Deficiency


Presentation

  • Patients usually present in first 6 months of life with respiratory/gastrointestinal tract infections and failure to thrive. Among the various types of severe combined immunodeficiency, enzyme deficiencies are relatively less common.[ncbi.nlm.nih.gov]
  • Clinical description SCID due to ADA deficiency has a variable clinical presentation.[orpha.net]
  • Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.[uniprot.org]
  • Case presentation A 14-month-old Arab boy had clinical features typical of severe combined immunodeficiency.[jmedicalcasereports.biomedcentral.com]
Malnutrition
  • Over time, affected individuals may develop chronic lung damage, malnutrition and other health problems. This process is due to changes in the ADA gene, located on the long arm of chromosome 20 (20q13.12).[ivami.com]
  • Over time, affected individuals may develop chronic lung damage, malnutrition, and other health problems. Adenosine deaminase deficiency is very rare and is estimated to occur in approximately 1 in 200,000 to 1,000,000 newborns worldwide.[ghr.nlm.nih.gov]
  • […] episodes of: Oral thrush Mouth ulcers Respiratory syncytial virus Rerpes simplex virus Varicella zoster virus Influenza Measles Adverse reactions caused by live vaccines (e.g. rotavirus, varicella) A family history of SCID Differential Diagnosis Extreme malnutrition[pedclerk.bsd.uchicago.edu]
Inguinal Hernia
  • Past surgical history included a left inguinal hernia repair. Flow cytometry (FCM) analysis was performed in order to quantify the number of B- T-, and NK-cells.[jmedicalcasereports.biomedcentral.com]
Recurrent Respiratory Infections
  • A few older patients have recently been diagnosed at 15-40 years of age with chronic pulmonary insufficiency due to recurrent respiratory infections, and other manifestations of immune deficiency and dysregulation [ 4 ].[jmedicalcasereports.biomedcentral.com]
Aspiration
  • Patients will also undergo bone marrow biopsy aspirate (as described above) twice a year. Patients will be followed once a year indefinitely to evaluate the long-term effects of therapy. ...[clinicaltrials.gov]
  • […] live vaccine against tuberculosis. bone marrow soft, spongy tissue located in the hollow centres of most bones that contains developing blood cells and cells of the immune system. bone marrow transplantation (BMT) transfer of bone marrow, obtained by aspiration[gosh.nhs.uk]
Failure to Thrive
  • Patients usually present in first 6 months of life with respiratory/gastrointestinal tract infections and failure to thrive. Among the various types of severe combined immunodeficiency, enzyme deficiencies are relatively less common.[ncbi.nlm.nih.gov]
  • The most common form presents in infancy with severe and recurrent opportunistic infections (including respiratory tract infections and candidiasis), failure to thrive, and usually results in early death.[orpha.net]
  • Clinical Findings If untreated, children born with SCID experience: Recurrent, severe infections including: Chronic viral diarrhea Mucocutaneous candidiasis Pneumonias secondary to: Pneumocystis jirovecii Adenovirus CMV Failure to thrive and death typically[pedclerk.bsd.uchicago.edu]
  • Infants born with SCID display failure to thrive and without proper treatment this condition is uniformly fatal early in life.[pathwaymedicine.org]
  • ., failure to thrive). Children with untreated SCID rarely live past the age of two.[genome.gov]
Long Arm
  • This process is due to changes in the ADA gene, located on the long arm of chromosome 20 (20q13.12). This gene encodes the enzyme adenosine deaminase. This enzyme is found throughout the body, but is more active on lymphocytes.[ivami.com]
  • The genomic sequence of ADA gene spans 32kb on the long arm of chromosome 20 and contains 12 exons [ 5 ]. More than 70 ADA mutations have been identified thus far.[jmedicalcasereports.biomedcentral.com]
Impulsivity
  • Pediatrics . 2016; 137 :e20152169 (DOI: 10.1542/peds.2015-2169 ) Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.[ada-scid.online]
Behavior Disorder
  • Patients may also present with extraimmune manifestations (including neurodevelopmental deficits, behavioral disorders, sensorineural deafness, and skeletal and hepatic abnormalities) as a result of the systemic nature of ADA expression.[orpha.net]
Onset at Age 4 Years
  • Ten to 15% of patients have a delayed clinical onset by age 6-24 months, and a smaller percentage have a partial form of ADA deficiency with later onset between ages 4 years and adulthood, both types showing less severe infections and gradual immunologic[orpha.net]

Workup

  • The patient was referred to Immunology Department of Armed Forces Institute of Pathology (AFIP), Rawalpindi for further evaluation and workup. Her Erythrocyte Sedimentation Rate (ESR) was 46 mm at 1st hour.[jpma.org.pk]

Treatment

  • However, due to some unavoidable limitations, enzyme treatment and chemotherapy were implemented.[fbme.utm.my]
  • The recommended treatment is based on allogeneic haematological stem cell transplantation (HSCT) from an HLA identical healthy sibling or close relative, which has a high success rate. However, most patients lack an identical donor.[evidence.nhs.uk]
  • Treatments can help, though, and people who get treatment before an infection happens can live long, healthy lives. Everyone has ADA genes. If you have ADA deficiency, you have a glitch (mutation) in yours.[webmd.com]
  • Management and treatment Treatment is based on allogenic hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy with pegylated adenosine deaminase enzyme or gene therapy by infusion of CD34 marrow cells that have been transduced with[orpha.net]

Prognosis

  • Prognosis Prognosis depends on the severity of the disease. Without treatment, SCID due to ADA deficiency that presents in infancy usually results in early death.[orpha.net]
  • Diagnosis - Adenosine deaminase deficiency Prognosis - Adenosine deaminase deficiency The long-term outlook (prognosis) for people with adenosine deaminase deficiency (ADA) varies depending on the severity of the condition, the timing of the diagnosis[checkorphan.org]
  • From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening[springermedizin.de]
  • , Prevention, and Complications Prognosis without intervention, death by 2 years patients 6 months of age who receive transplant have the best outcomes Complications severe infection death Please rate topic.[medbullets.com]
  • Prognosis There is no cure for SCID. Nearly all untreated patients die before age two, most before one year of age. Children who are treated with bone marrow transplants have a much better prognosis. Prevention There is no known way to prevent SCID.[healthofchildren.com]

Etiology

  • Etiology SCID due to ADA deficiency is caused by mutations in the ADA gene (20q13.11). The extraimmune manifestations are caused by toxic levels of purine metabolites that result from the deficiency of ADA.[orpha.net]
  • A variety of heritable genetic lesions can cause SCID and thus the disease is in reality a mixture of different genetic etiologies which manifest with similar clinical picture.[pathwaymedicine.org]
  • Researchers continue to identify SCID-associated gene defects; however, the genetic etiology remains unknown for a subset of clinically classified SCID patients.[aacc.org]

Epidemiology

  • Summary Epidemiology SCID due to ADA deficiency accounts for 10-15% of all cases of SCID. Its annual incidence is estimated to be between 1/200,000 and 1/1,000,000 live births. Both males and females are affected.[orpha.net]
  • EPIDEMIOLOGY Adenosine deaminase deficiency is very rare and is estimated to occur in approximately 1 in 200,000 to 1,000,000 newborns worldwide. This disorder is responsible for approximately 15 percent of SCID cases.[flipper.diff.org]
  • Rajabally YA, Simpson BS, Beri S, Bankart J, Gosalakkal JA (2009) Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population. Muscle Nerve 39:432-438.[autoimmunediseases.imedpub.com]
Sex distribution
Age distribution

Pathophysiology

  • Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children.[books.google.com]
  • Age of onset and severity is related to some 29 known genotypes associated with the disorder. [4] Pathophysiology [ edit ] ADA deficiency is due to a lack of the enzyme adenosine deaminase.[en.wikipedia.org]

Prevention

  • Your doctor may also prescribe antibiotics to prevent new infections. A baby or child with ADA-SCID may need to spend some time in an isolated hospital room, but his parents will be able to be with him.[webmd.com]
  • Identifying infants with this disorder early can help prevent their death at a young age.[merckmanuals.com]
  • Besides medicines and therapies to help prevent infections, other precautions are used. Children with SCID: are placed in isolation to help prevent the spread of infection should not get live vaccines.[kidshealth.org]
  • If the patient requires a blood transfusion, then irradiated (CMV-negative, leukocyte-depleted) blood should be given to prevent graft versus host disease due to T-cells in donor blood.[pediatriconcall.com]
  • Symptoms - Adenosine deaminase deficiency Causes - Adenosine deaminase deficiency Prevention - Adenosine deaminase deficiency Not supplied.[checkorphan.org]

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