Metabolic Newborn Screening

Question 1

How have the most common reasons for newborn death changed over the past century?

Answer 1

1900: diarrhea, gastrointestinal tract issues, flu, TB, premature birth or congenital anomalies
1960: postnatal asphyxia, prematurity, congenital anomalies, birth injury, Flu/pneumonia, accidents
2015: congenial anomalies/deformations/chromosomal abnormalities, extreme prematurity, SIDS, maternal complications during pregnancy, accidents/injuries

Question 2

What caused the drop in infant mortality?

Answer 2

presence of antibiotics, development of vaccines, improvement in nutrition, better education, improvement in sanitation

Question 3

what disease was the birth of newborn screening? describe it: genetics, clinical characteristics

How do we screen for this disease?

Answer 3

PKU - it is the gold standard by which all other metabolic diseases are judged

genetics: recessive condition resulting from mutations in the Phe hydroxylase gene
clinical: normal at birth, but over time develop progressive microcephaly, seizures, severe to profound intellectual impairment, eczema and loss of pigmentation
screen: Guthrie Test - blood spot cards…relatively reliable and robust blood collection and handling

Question 4

What is the difference between reactive and proactive tests? discuss cost and outcomes

Answer 4

reactive: tests performed after a patient is symptomatic from a disorder. these tend to be costlier on a per patient basis and result in poorer outcomes
proactive: screen detects disorder before it is symptomatic. these have cost incurred by every person and result in better outcomes

Question 5

What makes a good screen?

Answer 5

1. disease should be clinically severe or have severe consequences
2. natural history of disease is understood
3. effective treatment should be available and depend on diagnosis
4. disease incidence should be high enough to warrant screening
5. test should have a reasonably good sensitivity and specificity (rather have false positive instead of false negative)
6. screening test should be used by entire at risk population
7. adequate system for follow-up of positive results should be provided
8. economic cost-benefit analysis should favor screening and treatment

Question 6

How are the blood samples analyzed?

Answer 6

tandem mass spectrometry: measurement of the mass to charge ratio of charged particles

Question 7

what is classical galactosemia?

Answer 7

genetic: defect in galactose-1-phosphate uridyl transferase…autosomal recessive
clinical: infants will present with emesis, diarrhea, jaundice, sepsis, liver/kidney dysfunction, cataracts

cannot wait to treat this disease - give baby a soy based formula while repeat test and confirm diagnosis

Question 8

on the KS newborn screen, what are the main disorders checked for?

Answer 8

AA disorders (PKU), Hb electrophoresis, Fatty Acid Disorders (MCAD), Organic Acidemias (isovaleric aciduria: IVA, methylmalonic), other (galactosemia, CF, hearing, heart defects, hypothyroidism)

Question 9

What is MCADD?

Answer 9

medium-chain acyl CoA dehydrogenase deficiency

clinical: lethargy, hypoglycemic crisis, coma and seizures…baby not acting normal

see a lot of C8 carnitine….MCAD until proven otherwise when see a high spike

give baby sugar first - check for infections and confirm findings

Question 10

what is IVA

Answer 10

a defect in isovaleryl-CoA dehdrogenase

clinical: metabolic acidosis, hyperammonemia, hypoglycemia, decreased WBC and platelets; may smell of sweaty feet

worried about AA (abnormal C5) -> put baby on different formula that has less chained AA; can wait to see baby until the next day

Question 11

what is Krabbe disease

Answer 11

an autosomal recessive condition: caused by galactocerebrosidase deficiency

usually characterized by infantile-onset progressive neurologic disease (90%); other 10% present between 1-50ys

treatment: supportive care for symptomatic patients (bone marrow maybe but not a good option for obvi reasons)