NBS

Question 1

When did NBS start?

Answer 1

mid-1960s

Question 2

What was the first test avail for NBS?

Answer 2

PKU - they used dried blood spot for bacterial inhibition assay

Question 3

What 2 were added to NBS in 1970s?

Answer 3

congenital hypothyroidism and galactosemia

Question 4

What are 2 that AZ will be adding in 2022 to NBS?

Answer 4

X-linked Adrenoleukodystrophy
SMA

Question 5

What is the timing for NBS?

Answer 5

• so we get the sample at 24-72h old (24h better)
• then we get a second sample at 5-10d old

Question 6

What do you want to test for before blood transfusion?

Answer 6

• galactosemia
• Hemoglobinopathies

Question 7

How do we get the blood drops?

Answer 7

NOT sticking foot to the paper haha

really just poke and then drops onto paper

Question 8

How many confirmed positive can we detect on 1st screen? 2nd?

Answer 8

1st screen - 90%
2nd screen - 10%

*note AZ = 1/8 states who requires 2 tests

Question 9

Galactosemia best detected on what screen?

Answer 9

Any!

RBC enzyme assay not dep on time

BUT remember that it is INVALID if done after transfusion

Question 10

PKU and MCADD best detected on what screens?

Answer 10

either! pretty accurate for both

Question 11

VLCADD (Very long-chain acyl-CoA dehydrogenase deficiency) best detected on what screen?

Answer 11

1st

the reason is bc babies will not eat well for those 24h and rely on fat metab that we can detect

(since it is VERY LONG, better get going early on the FIRST screen)

Question 12

Homocystinuria best detected on what screen?

Answer 12

2nd

it is bc amylite protection is methionine, which rises much slower than other analyte

(note - Homocysteine = intermediary amino acid formed by the conversion of methionine to cysteine)

(boys who say NO HOMO don’t get a SECOND date)

Question 13

What is a method used to analyze NBS?

Answer 13

tandem mass spectrometry

goes through 2 MS to fragment these —> computer gives the data so we can look for peaks

Question 14

What is maybe most common thing detected on NBS?

Answer 14

hypothyroidism

Question 15

Propionic acidemia (PA) and Methylmalonic acidemia (MMA) present w ? on NBS

Answer 15

elevated C3

need more dx testing to distinguish between the 2

Question 16

What are some screening issues w Tandom Mass Spec?

Answer 16

1. false positives –> 0.1% = pos, then 90% are FALSE POS
2. Ambiguity of clinical pheno
3. cost of screening
4. treatment (not always easy/straightforward)

Question 17

What is an example of a ambiguous clinical pheno found on NBS?

Answer 17

3MCC
- so we used to say always IEM
- now we are like ok this is pretty common and maybe mild cases are a thing
- ex: mom had it not knowing her whole life, then baby tested pos bc it actually was just present in baby urine bc transported across the placenta

Question 18

What is the PPV for NBS?

Answer 18

10% overall

(bc 90% false pos)

Question 19

For what disorders is the PPV on higher end?

Answer 19

PKU
MCADD

Question 20

For what disorders is the PPV on lower end?

Answer 20

Cit (Citrullinemia) Type I (when ammonia accum in blood)

bc even carriers can have little elevated levels

Question 21

If there is high risk of decompensation, what referral do we need?

Answer 21

Genetics - bc this is likely a true positive

Question 22

What are common f/u labs for pos NBS?

Answer 22

• org acids
• amino acids
• acylcarnitines
• carnitine
• ammonia
• DNA studies

Question 23

? disorders tend to worsen over time

Answer 23

Amino acid (PKU, etc)

Question 24

? disorders tend to worsen over time, more variably though

Answer 24

Org acid disorders _ Urea cycle disorders

at Lab + Clinical level

Question 25

? disorders worsen when fasting?

Answer 25

Fatty acid disorders if newborn eating every 2-3 hours, not worry about decompensation

Question 26

What is an example on NBS that has poor response to treatment?

Answer 26

GA-2 (Glutaric acidemia type-2) = Fatty Acid ox disorder AND Org Acid disorder

Question 27

Risk of decompensation always present in what conditions?

Answer 27

MMA (Methylmalonic acidemia) PA (propionic acidemia) ---> can see cardiomyopathy MSUD

Question 28

Phenylketonuria (PKU) undx cases present w ? early on

Answer 28

DD in infancy or childhood can result in severe ID

Question 29

Incidence of PKU?

Answer 29

1/15,000

Question 30

Treatment for PKU?

Answer 30

phenylalanine restricted diet

Question 31

About 1% of those w PKU have?

Answer 31

Biopterin disorders --> this is a cofactor for phenylalanine hydroxylase (this req dif treatment than reg PKU)

Question 32

Galactosemia - what enzyme is high?

Answer 32

GALT enzyme high

Question 33

What can result from untreated Galactosemia?

Answer 33

liver failure cataracts sepsis ID death

Question 34

What is the prognosis for Galactosemia w treatment?

Answer 34

Good BUT risk for speech problems + Ovarian failure

Question 35

Medium-Chain Acyl-CoA Dehydrogenase Def (MCAAD) - what happens after depletion of liver glycogen?

Answer 35

rapid onset of severe hypoglycemia

Question 36

Incidence of Medium-Chain Acyl-CoA Dehydrogenase Def (MCAAD)

Answer 36

1/15,000 same as PKU

Question 37

Homocystinuria What NBS analyte do we detect?

Answer 37

Methionine most found on 2nd screen

Question 38

What are complications of Homocystinuria ?

Answer 38

Thrombotic problems liek strokes

Question 39

Treatment for Homocystinuria ?

Answer 39

B6 ---> 50% respond Low Met diet and Betaine --> if not respond to ^

Question 40

What happens in untreated MSUD?

Answer 40

metabolic crisis w severe cerebral edema

Question 41

Incidence of MSUD?

Answer 41

1/250,000 PA Mennonites 1/150

Question 42

If someone w MSUD has illness or too much protein intake, then what?

Answer 42

risk for decompensation (this is the time you would detect the smell)

Question 43

Treatment for MSUD?

Answer 43

restriction of branched chain amino acids