Expanded Newborn Screening Program

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Expanded Newborn Screening Program

State of Indiana
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Brought to you by the Indiana Chapter of the
March of Dimes
Saving babies, together
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Outline

• What is newborn screening?
• How newborn screening is performed
• Disorders screened in Indiana
• Expanded newborn screening using tandem mass
  spectrometry (MS/MS)
• Your responsibilities as a physician
• What is folic acid?

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What is newborn screening?
Newborn screening is a public health activity
that is performed on all newborns. Testing is
done by heel-stick shortly after birth for early
identification of those babies affected by
certain genetic, metabolic, hormonal and/or
functional conditions for which there is
effective treatment with early intervention.
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Newborn screening is a routine procedure for the
4 million babies born each year in the United
States.
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How newborn screening is performed

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Specimen Collection

• Using dried filter paper,
• blood samples are
• taken from the heel of the
• newborn prior to discharge
• from the hospital.

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The sample is submitted to the designated state
newborn screening lab that runs the tests and
reports back to the indicated primary care
physician/pediatrician. Invalid, abnormal, and
positive screens are also reported to the State
Newborn Screening Program for additional
follow-up.
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A Valid Screen...
Is one in which blood is drawn after the baby is
48 hours of age and has been on protein feedings
for 24 hours. Repeat screening is requested
when an invalid screening occurs.
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Repeat screening is required when
1) the specimen is collected before 24 hours of
protein feedings
2) the specimen is collected before the infant
is 48 hours of age
3) both 1 and 2
4) abnormal result occurs
5) presumptive positive result occurs
6) there is an unqualified specimen collection
(i.e. quantity not sufficient)
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However, the Indiana Newborn Screening Law 410
IAC 3-3-3) Sec. 3 (d) says
If the infant is discharged from the hospital
before forty-eight (48) hours after birth or
before being on a protein diet for twenty-four
(24) hours, a blood specimen shall be collected
regardless.
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Current Indiana Newborn Screening
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Current Disorders Included in Indiana Newborn
Screening
1. Congenital Adrenal Hyperplasia (CAH) 2.
Congenital Hypothyroidism (CH) 3. Biotinidase
Deficiency (BD) 4. Galactosemia (GAL) 5.
Homocystinuria (HCU) 6. Maple Syrup Urine Disease
(MSUD) 7. Phenylketonuria (PKU) 8. Sickle Cell
Anemia (SCA)
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Characteristics of Disorders Currently Included
in Indiana Newborn Screening

• Early detection and treatment significantly
  improve the outcome.
• All disorders require treatment for the life of
  the individual.
• Mild forms of the disorders may not be detected
  by Newborn Screening.

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Congenital Adrenal Hyperplasia (CAH)
CAH is most often caused by diminished activity
of an enzyme, 21 hydroxylase, that results in
failure of the formation of cortisol, a hormone
needed for stress and normal blood glucose
levels. Mild forms result in severe acne, excess
facial and/or body hair, early development of
pubic hair, and infertility in both males and
females.
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More severe forms of CAH can result in ambiguous
genitalia in a newborn girl. Males, however,
usually have normal genitalia and are less likely
to be diagnosed early. If not treated, CAH
can cause heart failure and death within a few
days of birth. Incidence 1 in 13,000 live
births
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Congenital Hypothyroidism (CH)
CH is a disorder caused by the under development
or under activity of the thyroid gland. Decreased
production of thyroid hormones prevents proper
body growth and psychomotor development.
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Physical signs of CH may not be recognized until
the infant is 3-4 months of age, at which time
irreversible brain damage may have already
occurred. Many times, early diagnosis of CH
relies almost solely on the results of the
newborn screening tests. Incidence 1 in 4,000
live births, which makes CH one of the most
common metabolic disorders.
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Biotinidase Deficiency (BD)
BD is caused by diminished activity of the enzyme
biotinidase that recycles and conserves biotin,
an important B vitamin. BD may cause serious
complications such as seizures, developmental
delay, mental retardation and hearing loss.
Untreated, the deficiency can lead to coma and
death.
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Infants with BD appear normal at birth, but then
develop symptoms after the first few weeks of
life. These symptoms include hypotonia, ataxia,
alopecia, seborrheic dermatitis, and optic nerve
atrophy. Incidence 1 in 65,000 live births
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Galactosemia
Babies with classic GAL have diminished activity
of galactose-1-phosphate uridyl transferase, a
liver enzyme needed to convert galactose, most
commonly found in milk products, into
glucose. Galactose then accumulates in the body
and causes damage in the vital organs leading to
blindness, severe mental retardation, infection,
and death. Incidence 1 in 40,000 live births
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Homocystinuria (HCU)
HCU is caused by diminished activity of the
enzyme cystathionine synthase, which is
responsible for converting the amino acid
homocysteine into cystathionine. This enzyme is
needed by the brain for normal development. If
undetected and untreated, HCU can lead to
seizures, delays in reaching developmental
milestones, mental retardation, and skeletal
abnormalities. Incidence 1 in 275,000 live
births
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Maple Syrup Urine Disease (MSUD)
MSUD affects the way the body metabolizes certain
small compounds of protein, the three branch
chain amino acids - leucine, isoleucine, and
valine. These amino acids accumulate in the blood
and cause a toxic effect that interferes with
brain function. The odor of maple syrup may be
noted in body fluids, hence the name for the
disorder. Incidence 1 in 250,000 live births
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Phenylketonuria (PKU)
PKU is a hereditary disease that results from
diminished activity of phenylalanine (phe)
hydroxylase, an enzyme that normally converts the
amino acid phenylalanine to tyrosine. This amino
acid can then accumulate and cause damage to the
brain, resulting in severe metal retardation.
Other findings include decreased pigmentation,
behavior problems, seizures and an unusual body
odor. Incidence 1 in 12,000 live births
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Sickle Cell Anemia
Sickle cell anemia is caused by decreased
oxygenation of red blood cells that causes the
cells to change shape from round and healthy to
rigid, sickle shape rods.
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This change in shape causes blockage of small
blood vessels, which results in severe pain,
damage to vital organs, stroke, and sometimes
death in childhood. Young affected children are
especially prone to severe bacterial infections
that can lead to septicemia, pneumonia, and
meningitis. Incidence 1 in 400 African-Americans
1 in 1,000 to 30,000 Hispanics
1 in 2,700 Native Americans
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Expanded Newborn Screening
A tandem mass spectrometer consists of two mass
spectrometers connected by a chamber, known as a
collision cell. Here molecules are broken
into pieces and the machine
then measures their weight, or mass.
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Each compound has a unique, specific mass
spectrum, which represents the fragments of the
compound that are generated by exposure to
ionization. The mass spectrometer electronically
measures the weight (mass) of the fragments,
quantifies the relative amount of each fragment
present, and displays it as a graph or spectrum.
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Biological testing for metabolic disorders
frequently employs one mass spectrometer in
combination with gas chromatography (GC/MS).
GC/MS testing usually analyses all the compounds
in the sample and takes about 20 minutes per
sample. It is less sensitive than tandem MS/MS.
Certain types of compounds, especially those seen
with disorders of fatty acid oxidation and some
organic acidemias, will not be detected by GC/MS,
but may be detected by MS/MS.
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By using MS/MS and setting the collision chamber
to allow only certain ions or fragments of
interest to pass, the second mass spectrometer
collects and displays data for a specific
compound.
The tandem mass spectrometer accomplishes this
task very quickly and accurately in about 2
minutes per sample.
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Specimen Collection to Treatment
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Using this expanded technology, Indiana will be
able to screen for an additional
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genetic disorders!
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These conditions include

Fatty Acid Oxidation Disorders

• Short Chain Acyl-CoA Dehydrogenase Deficiency
  (SCAD)
• Medium Chain Acyl-CoA Dehydrogenase Deficiency
  (MCAD)
• Very Long Chain Acyl-CoA Dehydrogenase Deficiency
  (VLCAD)
• 3-Hydroxy Long Chain Acyl-CoA Dehydrogenase
  Deficiency
• Carnitine Palmitoyl Transferase Deficiency

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Organic Acid Disorders

• Methylmalonic Acidemias
• Methylmalonyl-CoA Mutase Deficiencies
• Adenosylcobalamin Synthesis Defects (CbIA and
  CblB)
• Propionic Acidemia (Acute and Late Onset)
• Isocaleric Acidemia (Type 1)
• 3-Methylcrotonyl-CoA Carboxylase Deficiency
• 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency

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Continued...

• Multiple CoA Carboxylase Defience
• 3-Ketothiolase Defiency-both
• 2,4-Dienoyl-CoA Reductase Deficiency

Amino Acid Disorders

• Tyrosinemia I, II
• Citrullinemia
• Argininosuccinic Aciduria

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Two tandem mass spectrometry machines have been
purchased for the state of Indiana and full
implementation of the expanded screening began in
December, 2002.
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Your responsibilities as a Physician
Ensure that all newborns are screened prior to
discharge from the hospital. If you are sent a
letter regarding an abnormal or presumptive
positive test, please report back to the Indiana
State Department of Health if the infant in
question is not in your care. If the infant is in
your care, but you cannot reach the parents,
please also report this to the Indiana
State Department of Health.
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For more information on the additional
disorders or tandem mass spectrometry,
please contact the IU Newborn Screening
Lab/Tandem Mass Lab at 317.278.2606 or the State
Newborn Screening Program at 317.233.1231.
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Watch for more information to be sent from the
Indiana State Department of Health regarding the
state Newborn Screening Programs in early 2003.
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What is Folic Acid?
Folic acid is the synthetic form of a B vitamin
called folate that occurs naturally in certain
foods. Foods high in folic acid and folate
include fortified breakfast cereals, enriched
grain products, leafy green vegetables, oranges
and orange juice.
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Why is Folic Acid Important?
It may help prevent certain birth defects.
Neural tube defects, or NTDs, are birth defects
of the brain and spinal cord. If all women of
childbearing age took 400 mcg of folic acid
daily, before and during early pregnancy, it
could help reduce the number of NTD-affected
pregnancies by up to 70.
Some studies suggest that folic acid may also
help protect individuals from heart disease and
some cancers, including cervical, colon, and
possibly breast.
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Why is this Important for Health Care
Professionals? According to the 2002 Gallup
Survey conducted by the March of Dimes, 34 of
women who do not currently take a vitamin or
mineral supplement said they would be very likely
to take a daily multi-vitamin if their physician
or other health care provider advised them to.
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What can you do?

• Talk to your patients about folic acid!
• Encourage them to take a multi- vitamin that
  contains folic acid or a folic acid supplement
  every day
• Find out more about folic acid by visiting
  www.marchofdimes.com

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This CD made possible through the support of
The Donald E. Nancy M. Smith Foundation Carmel
Care Center - Carmel, IN Rawlins House -
Pendleton, IN Countryside Manor - Anderson,
IN Harbour Manor - Noblesville, IN Indiana
State Department of Health
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Power Point presentation by
Jacquelin Krasner, March of Dimes Intern
Under leadership of Janet Estes, State Director
Indiana Chapter March of Dimes Melody
Stevens, State Director of Program Services
Public Affairs