SCID:
A Pediatric Emergency
Rebecca H. Buckley
Severe combined immunodeficiency (SCID) is a syn-
drome 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 recon-
stitution 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 hematopoi-
etic 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, implemen-
tation 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 rec-
ommendation 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
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Human Services in 2010. Currently, all 50 states have
added screening for SCID and other forms of T cell lym-
phopenia 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 phy-
sician regarding appropriate care of the infant while evalu-
ations 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 syn-
drome (usually only the complete DiGeorge syndrome),
ataxia telangiectasia, trisomy 21, CHARGE syndrome, con-
genital cardiac syndromes, other congenital anomalies,
and vascular leakage syndromes. Many of the borderline
and some of the abnormal results are due to prematu-
rity. 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
55
 it through a capillary tube.
In the past, a majority of the conditions screened for in
newborn screening panels have been metabolic or endo-
crine disorders or hemoglobinopathies. With the avail-
ability 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 ben-
efit 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 recom-
mendations 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 implementa-
tion of screening actually saves the state money because
it reduces costs for Medicaid and other third-party pay-
ors 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.
Rebecca H. Buckley, MD J. Buren Sidbury professor of Pediatrics and
professor of Immunology, Duke University Medical Center, Durham,
North Carolina.
Acknowledgments
Potential conflicts of interest. R.H.B. has no relevant conflicts of
interests
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Electronically published January 14, 2019.
Address correspondence to Rebecca H. Buckley, 426 Jones Building,
Duke University Medical Center, Durham, NC 27710 (rebecca.buckley
@duke.edu).
N C Med J. 2019;80(1):55-56. ©2019 by the North Carolina Institute
of Medicine and The Duke Endowment. All rights reserved.
0029-2559/2019/80113