ADA-SCID (adenosine deaminase-deficient SCID)

ADA-SCID stands for adenosine deaminase–deficient severe combined immunodeficiency. It is one type of SCID, a group of genetic conditions in which a baby is born without a working immune defense. In ADA-SCID, T cells, B cells and natural killer (NK) cells are all very low. NK cells are another kind of white blood cell that fights infection.

ADA-SCID is more than an immune problem. It can also affect the lungs, liver, bones, kidneys, brain and hearing. A smaller group of people have a milder form that shows up later in childhood or beyond. Their care can differ from that of babies with classic SCID.

ADA-SCID is caused by changes in both copies of the ADA gene. This gene carries the instructions for adenosine deaminase, an enzyme (a protein that speeds up a chemical reaction in the body). Without it, a waste product called deoxyadenosine builds up. Developing lymphocytes, the family of white blood cells that includes T, B and NK cells, are especially easily harmed.

The condition is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy and has no symptoms. When both parents are carriers, each pregnancy has a 1 in 4 chance of a child with ADA deficiency. Genetic testing confirms the diagnosis and lets a genetic counselor explain what it means for the family.

Babies with ADA-SCID usually look healthy at birth. Without treatment, they develop severe, repeated infections and often poor growth in the first months of life. Germs that most babies shrug off can become life-threatening. Some also have low neutrophils, bone changes, liver problems or a sudden breathing illness caused by protein filling the lungs’ air sacs.

Where it is offered, newborn screening for SCID can find most babies with ADA-SCID before they get sick.

Finding the condition early lets doctors start protection and treatment before serious infections take hold. In rare cases, a milder, later-onset form can pass the newborn screen, so later warning signs such as repeated infections still deserve attention.

Before a lasting treatment, families protect the baby at home from crowds and sick people. Care usually includes immunoglobulin, which is antibodies from donated plasma, plus medicines to prevent pneumonia and fungal infections. If the mother carries CMV, a common virus, doctors may advise pausing breastfeeding.

Enzyme injections mean regular clinic visits and blood tests to check enzyme levels and toxic byproducts. A transplant or gene therapy then brings a hospital stay in isolation while new immune cells grow. Gene therapy can mean travel to a distant center, and immune recovery after it may take many months.

Follow-up continues for years after any treatment. Children are checked for growth, development, hearing, lung and liver health, and for how well the immune system is holding up.

Soon after diagnosis, doctors check the HLA type of the child and close family members. A matched relative is the preferred donor. Gene therapy needs no donor at all, because it uses the child’s own stem cells.

Sometimes neither a matched relative nor gene therapy is available, or a first treatment does not work. Then doctors consider a matched unrelated donor or a half-matched (haploidentical) family member. Results with these donors have been less good than with a matched sibling, though methods continue to improve. Because long-term enzyme therapy is not recommended, experts advise planning for this option early.

A registry volunteer can matter to a child who needs an unrelated donor. For ADA-SCID, though, the specialist team first weighs enzyme therapy, a family donor and gene therapy. Joining a registry cannot promise a match for any one child.