Newborn Screening for SCID in a High-Risk Population

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DESCRIPTION (provided by applicant): Severe combined immunodeficiency (SCID) is a rare, but life-threatening inherited disorder in which infants are born without T or B cell function. They develop serious infections in their first months of life and do not survive past infancy unless they receive immune-reconstituting treatment, such as a hematopoietic stem cell transplant (HSCT) from a healthy person. Infants diagnosed with SCID soon after birth, and before developing infections, have the best chance of survival and fewer medical complications. To recognize SCID before onset of infections, however, requires universal screening of newborns. Dr. Puck has developed an assay for T cell lymphocytopenia based on quantitating T-cell receptor excision circles (TRECs) in DNA extracted from dried blood spots. TRECs are present in newly formed T cells, but essentially absent in the blood of infants with SCID, in whom T cell maturation is impaired. A pilot clinical trial to establish feasibility of prospective, population-based TREC screening is planned. With maternal informed consent, screening for SCID will be offered to infants born in 2 hospitals on the Western Navajo Reservation in Arizona. We plan a SCID screening trial here for 5 reasons: 1. SCID is a serious condition not readily apparent at birth for which early diagnosis can improve health outcome. 2. Navajo infants have at least a 20-fold higher incidence of SCID than the general population because of an ARTEMIS gene mutation found in individuals of Athabaskan ancestry. Around one per 2,000 Navajo births is affected with SCID, increasing the likelihood of finding SCID in a trial of limited size. 3. Effective local public health and outreach programs are in place on the Navajo Reservation to assure communication with families for follow-up when indicated. 4. Navajo infants diagnosed with SCID receive their bone marrow transplants at the UCSF Children's Hospital in the program of Dr. Cowan, a world authority on treatment of all SCID, and particularly ARTEMIS SCID. Dr. Cowan and Dr. Hu track the outcomes of the Navajo SCID patients. 5. The TREC assay methodology needs to be validated in population-based studies to establish sensitivity and specificity. A trial in a population with a high incidence of SCID is the most efficient means to measure test validity. PUBLIC HEALTH RELEVANCE: Babies with severe combined immunodeficiency (SCID) are unable to fight infections. They become severely ill in their first months of life and do not survive unless their immune systems can be restored. SCID can be treated by bone marrow transplant if recognized early. We are working on a newborn screening test designed to diagnose SCID before infections occur. We will conduct a pilot testing program in a high-risk population on the Navajo Indian Reservation, where 1 in 2,000 infants is born with SCID.