FEATURE
“The easy disorders have already
been done”
Currently, virtually all of the four million
or so babies born in the United States each
year receive NBS within the first 24 to 48
hours of life. Since 97% of this screening
is the responsibility of state public health
laboratories (PHLs), PHL scientists have
spearheaded the implementation of new
screening technologies and generally
embraced the expansion of screening
panels. But as NBS candidate disorders
become rarer and rarer, their diagnosis
less clear-cut, and their treatments less
effective, NBS advocates have grappled
with what Michele Caggana, ScD, FACMG,
calls the “push and pull of adding new
conditions.”
Caggana, who heads the NBS Program
and the Genetic Testing Quality Assurance
Program at New York’s Wadsworth
Center—the state PHL—said, “New York
has always been an early adopter” of
NBS candidate conditions, just last year
adding SMA, mucopolysaccharidosis
Type I (MPS-I) and guanidinoacetate
methyltransferase deficiency to its
screening panel. Yet, she said, “We have
to be thoughtful about how we do NBS
expansion. The low hanging fruit, the easy
disorders, have already been done.”
One unresolved issue, said Patrick
Hopkins, the semi-retired former NBS
chief at the Missouri State Public Health
Laboratory, is the “growing challenge of
deciding on what we’re screening for,
such as newborn disorders, childhood
disorders and late onset disorders. Often
we cannot safely sort out the difference
between these on the screening test,
and if we could, where would we draw
the line?”
Pompe disease, for example, has a classic
infantile form, requiring immediate
intervention, and later onset forms (about
72% of cases) in which serious symptoms
may be delayed until adulthood. Babies
with either of these variants will screen
positive for Pompe, as well as babies
with a less-urgent, non-classic infantile
form and babies with pseudo-deficiency,
who have biochemical Pompe disease
markers, but will never go on to develop
the disease. Follow-up providers must
determine the appropriate diagnosis and
counsel families based on limited clinical
guidance, since there is little medical
experience with Pompe, especially over
the long term.
Molecular testing raises similar issues.
Now used for discrete NBS applications—
mostly second or third tier testing—it is
expected to become more prominent in
the NBS laboratory.
Said Caggana, “What we’re seeing with
molecular [technology]—the ability to
multiplex and look at several different
genes at once—harkens back to when
mass spectrometry came on the scene
[in the early 2000s].... It really pushed
the field.”
Yet molecular testing comes with its
own challenges, including the need for
added infrastructure (including new
instrumentation, a dedicated “clean”
room and space to accommodate a
unidirectional flow of testing), highly
specialized staff training and capacity to
analyze massive amounts of genetic data.
Moreover, Caggana noted that “no one’s
assessed molecular [findings] on a broad
stroke of the population of healthy babies”
to inform data analysis and interpretation
of novel gene variants.
Kimberly Noble Piper, RN, CPH, CPHG,
genetics coordinator for the Iowa
Department of Public Health (IDPH)
said molecular screening “comes with a
Babies Saved Here: Patrick Hopkins
and Mark Temple in the Missouri LSD
Testing Laboratory. Photo: MO PHL
6
LAB MATTERS Spring 2019
PublicHealthLabs
@APHL
APHL.org