Congenital Immunodeficiencies and AIDS/HIV

What is it?

Severe Combined Immunodeficiencies (SCIDs) are a group of primary immunodeficiencies, usually hereditary, characterized by a numerical and functional defect in T and B lymphocytes.
Children with these diseases have growth defects and repeatedly contract bacterial, viral, and opportunistic pathogen infections.
Genetic alterations underlying SCIDs have been identified in most cases and can be expressed as a defect in:

  • lymphocyte receptors;
  • molecules responsible for the transmission of intracellular signals;
  • transcription factors;
  • enzymes of the purine metabolic pathway such as adenosine deaminase (ADA) and purinenucleoside phosphorylase (PNP)

The incidence of SCIDs varies between 1/50000 and 1/75000 births.

SCID-ADA (Severe Combined Immuno Deficiencies)

It is a severe congenital immunodeficiency due to genetically determined deficiency of adenosine deaminase (ADA). ADA is a ubiquitous enzyme the deficiency of which leads to a generalized metabolic toxicity, but with the most deleterious effects on the lymphatic system: the result is a progressive deterioration of immune function.
It is the cause of about 25% of SCID cases.

Which are the symptoms?


  • early detection after birth of B and T lymphopenia;
  • deficits in humoral and cellular immunity;
  • growth arrest;
  • fungal, viral, and opportunistic microorganism infections.

In addition to the immune defect, about 50% of patients show skeletal alterations of the chondro-costal junctions, such as dimpling and convex outward curvature, recognizable by radiography in lateral projection.

How is it diagnosed?

Specific diagnostic insights are based on the assay of ADA within red blood cells and lymphocytes. Prenatal diagnosis can be performed on chorionic villus samples, amniotic fluid cells, and fetal blood by evaluation of enzyme activity.

How is it treated?

With initial isolation in a sterile hospital setting, broad-spectrum antibiotic therapy is administered in combination with intravenous immunoglobulins and intravenous nutrition.
Specific therapy consists of:

  • allogeneic marrow transplantation;
  • exogenous enzyme replacement therapy;
  • gene therapy.

For marrow transplantation, only about 30% of patients have a compatible family donor. Transplantation from a haploidentical donor and transplantation with a non-family HLA-identical donor do not produce the same results.
Exogenous enzyme replacement therapy is based on the intramuscular administration of bovine-derived ADA. Treated children exhibit normal growth, development, response to common exanthematous infections, absence of opportunistic infections.
Clinical response is good, although about 65% of patients after one year of therapy produce antibodies directed against bovine enzyme.
Very high cost and parenteral route of administration are aspects that make this therapy not always easily available and manageable. Furthermore, despite the recent introduction of this therapy into the clinic, questions remain about its long-term efficacy.
Finally, gene therapy aims to modify the genetic information of cells by inserting the normofunctioning gene, which produces the ADA enzyme, into peripheral lymphocytes, bone marrow stem cells and progenitors from umbilical cord blood.
SCID-ADA was the first genetic disease considered for this type of treatment. Gene therapy program in collaboration with the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) is operating at this unit.

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Where do we treat it?

Within the San Donato Group, you can find Congenital Immunodeficiencies and AIDS/HIV specialists at these departments:

Are you interested in receiving the treatment?

Contact us and we will take care of you.