An examination of a study underlining newborn screening and severe combined immune deficiency.

1. Newborn Screening
and Severe
Combined Immune
Deficiency
Dr. Allen Cherer

2. April (April 22-29) has been designated as
National Primary Immunodeficiency
Awareness Month and provides an
opportunity to better understand the more
than 250 rare, genetic disorders in which
the body’s normal immune system is
absent or functions improperly. Since an
important function of the immune system
is to protect against infection, patients
with primary immune deficiency have an
increased susceptibility to infection.

3. Severe Combined Immune Deficiency
(SCID), popularized in the 1976 movie
“The Boy in the Plastic Bubble”, is
generally considered to be the most
serious of the primary
immunodeficiencies.

4. There are at least 13 different genetic
defects that can cause the disease; all
of which are present at birth, involve
missing T lymphocytes which are
important in identifying and attacking
perceived “invaders”, and affect the
function of B lymphocytes which
produce antibodies against infection.

5. The absence of T lymphocytes and
antibody immunity results in severe
infections, diarrhea, and failure to
thrive. Regardless of the genetics,
patients invariably succumb to an early
death due to overwhelming infection.
New approaches to diagnosis and
management have changed what at
one time was a dismal prognosis.

6. Treatment options have come a long
way over the past 4 decades and include
enzyme replacement, bone marrow
transplant, and gene therapy. Paramount
to this change is early diagnosis before
the infant has had a chance to develop
any serious infections.

7. The most effective therapy to date is
immune reconstitution via stem cell
transplant which has been shown to be
highly successful (94%) if performed by
3.5 months of age. Hence, timing is
crucial in terms of diagnosis and
treatment.

8. Typically, infants with SCID appear
totally normal at birth and have no
family history of immunodeficiency. In
the past, patients were primarily
identified either by previous family
history, physical manifestations, or
after onset of life-threatening
infection.

9. Early identification of SCID has been
achieved through the use of the 7-cell
receptor excision circle (TREC) assay
as part of the routine newborn
screening program.

10. Absent or low TREC levels can indicate
insufficient T lymphocyte production
characteristic of SCID, as well as low T
lymphocyte, non-SCID conditions as
seen in DiGeorge Syndrome, Trisomy
21, CHARGE Syndrome, and ataxia
telangiectasia. On May 21, 2010, The
U.S. Department of Health and Human
Services (HHS) recommended that
every state include the assay as part of
the newborn screen.

11. In the landmark study based on
retrospective data on more than 3
million infants from 11 newborn
screening programs using the TREC
methodology conducted by Jennifer
Puck, MD and colleagues and
published August 20, 2014 in The
Journal of the American Medical
Association, the value of early
detection and treatment of SCID was
confirmed.

12. In addition, the study found an
incidence rate almost twice as great (1
in 58,000 births) as had been previously
estimated. Since the point of newborn
screening is to identify conditions for
which early treatment is life-saving, the
study was a crucial step in the
adoption of universal screening.

13. As of April 1, 2016, all, except for 11,
states have adopted routine newborn
screening programs for SCID. A 2016
study published in the Journal of
Pediatrics by Ding and others provided
an eloquent cost-benefit analysis of
newborn screening in the treatment of
Severe Combined Immune Deficiency.

14. Based on data obtained from 86,000
infants in Washington state, the study
showed that newborn screening for
SCID is clearly cost-effective. Hopefully,
the study provides additional support in
economic terms for the adoption of
universal screening programs in all 50
states.