IL7R-deficient SCID

SCID stands for severe combined immunodeficiency. It is a group of rare genetic conditions in which a baby is born without a working immune system. IL7R deficiency is the fourth most common type, according to the Immune Deficiency Foundation. It causes about 1 in 10 cases.

Babies with IL7R-deficient SCID have few or no T cells. Unlike some other types, they have normal or even high numbers of B cells, which make antibodies, and natural killer (NK) cells, which attack virus-infected cells. Doctors call this pattern T-B+NK+ SCID.

Normal numbers of some immune cells can be misleading. Without T cells to guide them, B cells cannot make useful antibodies, so the baby is still at risk of severe infection. Some changes in the IL7R gene cause a rare, overactive immune state called Omenn syndrome instead of typical SCID.

IL7R-deficient SCID is caused by changes in the IL7R gene. This gene makes one part of the receptor for interleukin 7 (IL-7), a signal that young immune cells need to develop. Without that signal, T cells cannot form normally.

The condition is autosomal recessive. A child is affected only when both copies of the gene have a change, one from each parent. Parents who carry one changed copy usually have no symptoms. When both parents are carriers, each pregnancy has a 1 in 4 chance of an affected child, a 1 in 2 chance of a carrier child and a 1 in 4 chance of a child with neither change.

Once the family’s gene changes are known, relatives can have carrier testing and a pregnancy can be tested before birth. A genetic counselor can explain what the results mean for brothers, sisters and future children.

Babies look healthy at birth. Without treatment, symptoms start in infancy. They include infections that keep coming back, fever, ongoing diarrhea, skin inflammation and poor weight gain and growth.

In the United States, newborn screening for SCID reached every state by the end of 2018. A heel-prick blood test called TREC checks for signs that the baby is making new T cells, so babies with IL7R-deficient SCID can be found before they get sick. Where screening is not available, the condition is usually found only after serious infections begin.

An abnormal screen is not a diagnosis, but it needs urgent attention from an immunology team. Blood tests count each kind of immune cell, and genetic testing confirms the cause. Speed matters: in a large study in the United States and Canada, babies who had an active infection when they were transplanted were less likely to survive.

The weeks between diagnosis and transplant can be frightening. Families are usually asked to keep the baby at home or in hospital, away from crowds, daycare and anyone who is sick, even with a cold. Brothers and sisters who go to school or daycare can bring germs home, so daily routines often change for the whole family.

Treatment means a stay at a specialist children’s hospital, sometimes far from home. Afterward, checkups continue for years to see how well the donor cells have taken hold and how the child is growing. Preventive medicines and antibody replacement are stopped only when the new immune system is working well. Vaccines are given after that, on the team’s schedule.

Because the condition is recessive, parents may also face decisions about testing their other children and planning future pregnancies. Talking with other SCID families, a genetic counselor and the hospital’s social workers can help with the stress, the isolation and the practical costs.

A transplant for IL7R-deficient SCID uses blood-forming stem cells from a donor. A brother or sister who is a full HLA match is the first choice. But each full sibling has only about a 1 in 4 chance of being a match, and siblings are also checked to make sure they do not have the condition themselves. Many children do not have a matched sibling.

Without one, teams look for a fully matched unrelated donor through the registries. If that search would take too long for the baby’s safety, or no match exists, a half-matched family member, usually a parent (a haploidentical donor), or a cord blood unit is used instead. In a large study in the United States and Canada, survival was high with every donor type when babies were transplanted young or before infections set in.

This is why registry volunteers matter for SCID, and why speed matters. A matched volunteer who is ready to donate quickly can make an unrelated transplant possible while a baby waits in protective isolation. Joining a registry cannot promise a match for any one child, and many children are treated with a parent’s cells instead.