Artemis-deficient SCID (DCLRE1C)

Artemis is a protein that helps repair breaks in DNA. Developing T and B cells rely on that repair step to finish building the receptors they use to recognize germs. Without working Artemis, these cells cannot mature, so babies are born with almost no T or B cells. Natural killer (NK) cells, another kind of infection-fighting white blood cell, are still present.

Unlike most types of SCID, Artemis deficiency affects every cell in the body, not only immune cells. Cells are unusually sensitive to radiation and to a group of chemotherapy drugs called alkylating agents, which is why it is sometimes called radiosensitive SCID. Milder, “leaky” forms with some Artemis activity can cause Omenn syndrome or immune problems that appear later.

Artemis-deficient SCID is caused by changes in both copies of the DCLRE1C gene, which carries the instructions for Artemis. It is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy without symptoms, and when both parents are carriers, each pregnancy has a 1 in 4 chance of an affected child.

A 2022 medical report put it at only about 2 or 3 of every 100 SCID cases. It is much more common among Navajo and Apache people, many of whom share one inherited change passed down over generations. For that reason it has also been called Athabascan-type SCID. It is also seen more often in communities where parents are commonly related by blood.

Babies usually seem healthy at first. Without treatment, they develop severe infections, ongoing diarrhea, thrush and poor growth in the first months of life, and common viruses can become life-threatening. Some develop mouth sores that are not caused by infection, and some develop autoimmune problems that attack red blood cells or platelets.

Where newborn screening for SCID is offered, it can find babies with Artemis SCID before they are sick. Knowing that the cause is Artemis matters, because it changes how a transplant is planned.

The aim is to treat before serious infection starts. A study followed 902 children with SCID who had transplants in the United States and Canada from 1982 to 2018. Active infection and older age at transplant were linked to lower survival. In that study, SCID types caused by DNA-repair problems, including Artemis, had lower survival than the most common type. Not every study has found this difference.

Before transplant, families protect the baby from crowds and sick people. Care usually includes immunoglobulin, which is antibodies from donated plasma, and medicines to prevent pneumonia and fungal infections. This care usually takes place at a specialist children’s transplant center, which can mean travel.

After transplant, children need years of follow-up. Growth, dental development and hormone levels are checked, and some children need immunoglobulin for a long time if B cells do not recover. In a study comparing children after transplant, those with Artemis SCID had more infections over the long term than those with RAG SCID. Ongoing care matters even when the transplant has worked.

Most children with Artemis SCID need blood-forming stem cells from a donor. A matched brother or sister is the first choice, and siblings are checked for the condition as well as for their HLA type. If there is no matched relative, European guidelines name a fully matched unrelated donor as the next option.

Because SCID is an emergency, the donor search starts as soon as the diagnosis is made. If a matched unrelated donor cannot be found quickly enough, a half-matched (haploidentical) parent or a partly matched cord blood unit may be used instead. In Artemis SCID, donors other than a matched sibling carry higher risks of graft rejection and graft-versus-host disease.

Registry volunteers make unrelated-donor searches possible. A registration cannot promise a match for a particular child, and the transplant team chooses the safest suitable donor at the time.