Newborn Screening

Question 1

List 3 characteristics of a disorder appropriate for newborn screening

Answer 1

1. Feasible means of early detection (24-48 hours after birth) when it would NOT normally be detected by exam
2. Good sensitivity and specificity of test
3. Benefits of testing (treatability of the disease, ability to start treatment in presymptomatic/early stages)

Question 2

What type of hypothyroidism is missed by most newborn screening assays?

Answer 2

Central hypothyroidism (when TSH is measured)

Question 3

What lab methods are used in newborn screening?

Answer 3

• Bacterial inhibition assay (BIA) - ex. PKU, galactosemia, maple syrup urine disease, homocystinuria
• Flurometric and Photometric tests - ex.PKU, galactosemia, G6PD, biotidinase deficiency, lysosomal storage disease
• Immunoassay - ex. CAH, congenital hypothryoidsim
• MS/MS (Tandem Mass Spectrometry) - ex. CAH, acylcarnitine, amino acidopathies, FAOD
• Molecular Genetic Analysis - ex. CF (not yet used as primary screening but as second tier test)

Question 4

What types of CAH may be missed by standard newborn screening?

Answer 4

• 17 alpha hydroxylase/17,20-lyase deficiency
• StAR deficiency

Because 17OHP is not elevated

Question 5

What types of CAH are picked up by standard newborn screening?

Answer 5

• 21 hydroxylase deficiency
• 11 beta hydroxylase deficiency

Because 17OHP is elevated

Question 6

Why is false positive newborn screen common in premature neonates?

Answer 6

Cross reactivity of steroid compounds related to 17OHP. Therefore reference ranges are adjusted for premies

Question 7

What the most common reason for false positive screen for congenital hypothyroidism

Answer 7

Sample collected too early (<24-48 hours)

Question 8

List 2 reasons why preterm infants may have falsely low levels of 17OHP

Answer 8

1. On cortisol therapy
2. Mother received betamethasone before delivery

Question 9

Name 2 reasons for missed classic CAH on newborn screening

Answer 9

1. Decreased inactivation of maternal cortisol by placental 11 beta-hydroxysteroid dehydrogenase
2. Increased senstivity of the fetal HPA axis to maternal cortisol leading to delayed rise of 17OHP in first 24-48 hours