Metabolic Disorders and Screening

Question 1

What metabolic diseases are being screened for at the 6 day Guthrie Heel prick test?

Answer 1

1. Phenylketonuria
2. congenital hypothyroidism
3. cystic fibrosis
4. sickle cell disease
5. MCAD (medium chain acylCoA dehydrogenase) deficiency

Question 2

What is phenylketnuria?

How is it screened for?

Answer 2

Genetic metabolic disorder with Phenylanine hydroxylase deficiency leading to built up of Phenylalanine levels (screening test), which is toxic at higher levels

Relatively common: 1:10.000

Question 3

What is the clinical presentation of children with untreated phenylketnuria?

Answer 3

phenylketnuria = toxic at high levels

Presents with IQ<50

Question 4

What is the sensitivity of a test?

Answer 4

Sensitivity is the probability that someone with the disease will correctly test positive

TP/(TP+FN)
* 100 people with CF in total, and 90 actually test positive. Sensitivity is 90/100=90%

Question 5

What is the specificity of a test?

Answer 5

Specificity is the probability (in %) that someone without the disease will correctly test negative o TN/(FP+TN)
* 85 people without CF in total, and 80 actually test negative. Specificity is 80/85=94% (much easier to think like this than memorise formulae!)

Question 6

What is the positive predictive value of a test?

Answer 6

PPV is the probability that someone who tests positive actually has the disease (dependant on disease prevalence)

• TP/(TP+FP)
  95 people tested positive, of which 90 had the disease PPV= 90/95= 95%

Question 7

What is the Negative predictive vale of a test?

Answer 7

NPV is the probability that someone who tests negative actually doesn’t have the disease
TN/(TN+FN)
90 people tested negative, of which 80 didn’t have the disease, NPV= 80/90= 89%

Question 8

What biological marker is used for detection of congenital hypothyroidism?

Answer 8

TSH (high) on screening test (PPV 60%)

Question 9

What biological marker is used for detection of CF in neonatal screening?

Answer 9

Immune reactive trypsin positive → DNA mutation
detection (

Question 10

What biological marker is used for detection of Medium Chain AcylCoA dehydrogenase Deficiency in neonatal screening?

What is the main clinical problem?

Answer 10

Acylcarnitine levels by tandem Mass Spectrometry

Fatty acid metabolism disorder –> Might cause cod-death (due to hypoglycaemia)

Question 11

Continue with Table in Path guide with most important abnormalities