SCID

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by an absence of T cells, resulting in a profound deficiency of adaptive immune function. This condition is uniformly fatal in the first two years of life unless immune reconstitution can be accomplished. Early recognition of SCID should be considered a pediatric emergency [1], because a diagnosis before live vaccines such as rotovirus [2, 4] or non-irradiated blood products are given and before the development of infections permits lifesaving hematopoietic stem cell transplantation [5-8], enzyme replacement therapy [9], or gene therapy [10-12]. However, most SCID infants appear physically normal at birth and until they begin to develop infections, then failure to thrive begins. In most cases, there is no family history of SCID. If SCID is not detected until the infant is older, there is a much higher likelihood that death will occur before successful definitive therapy can be achieved.

The need for newborn screening for this condition has been recognized for the past 21 years. However, implementation of screening required development of an assay for T cell lymphopenia that could be performed on dried blood spots that have been routinely collected from newborn infants for the past 54 years. This test development was accomplished eight years ago and shortly thereafter a recommendation was made to the US Department of Helath and Human Service Secretary's Advisory Committee on Heritable Disorders of Newborns and Children to add SCID and other forms of T cell lymphopenia to the routine newborn screening panel. This was approved unanimously by the Committee and then by the Secretary of Health and Human Services in 2010. Currently, all 50 states have added screening for SCID and other forms of T cell lymphopenia to their routine newborn screening panel.

The results of screening for T cell lymphopenia are reported to the primary care provider as either normal, abnormal, or borderline. If abnormal, the infant should see an immunologist within three days after having been seen by the primary care provider. If borderline, the physician will be asked to submit a second dried blood spot within 24 hours. In both cases, a set of instructions from the state newborn screening follow-up office will be sent to the physician regarding appropriate care of the infant while evaluations are being performed.

The infant should not be referred directly to a bone marrow transplant service because, as noted above, other non-SCID causes of T cell lymphopenia are detected by this screening test. A majority of these conditions will probably require different forms of treatment than those needed for SCID infants. This is the paramount reason that an immunologist is needed to determine the precise cause of the T cell lymphopenia and ultimately the appropriate treatment. Among the most frequent conditions other than SCID detected by this screening are DiGeorge syndrome (usually only the complete DiGeorge syndrome), ataxia telangiectasia, trisomy 21, CHARGE syndrome, congenital cardiac syndromes, other congenital anomalies, and vascular leakage syndromes. Many of the borderline and some of the abnormal results are due to prematurity. Abnormal and borderline results could also be due to technical problems such as drawing the blood for the dried blood spot through a heparinized central line or collecting it through a capillary tube.

In the past, a majority of the conditions screened for in newborn screening panels have been metabolic or endocrine disorders or hemoglobinopathies. With the availability of modern molecular technology, it is likely that in the future many other types of genetic diseases will be screened for and detected at birth.

SCID and other forms of T cell lymphopenia are the first group of genetically determined immunologic disorders to be screened for. There are now 354 recognized inborn errors of immunity and the abnormal genes are known for 344 of them [13]. All of these conditions would benefit from early diagnosis before life-threatening infections develop, so it is clear that detection at birth would be ideal.

Resistance by individual states to adapt the recommendations of the HHS Secretary's Advisory Committee for additions to the Routine Screening Panel is almost always due to cost issues. In most cases the implementation of screening actually saves the state money because it reduces costs for Medicaid and other third-party payors that provide treatment for infants and children with serious or life-threatening infections. Prevention of such infections is even more important because permanent and significant organ damage can occur from them even if the infant survives.

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