Chempath 5: Metabolic disorders and screening 1

Question 1

List the 9 diseases that are tested for in newborns with the Guthrie heel prick test ?

Answer 1

Congenital hypothyroidism
Sickle cell disease
Cystic fibrosis 
Maple syrup urine disease (MSUD)
Phenylketonuria (PKU)
Homocystinuria (HCU)
Medium chain acyl-CoA dehydrogenase disease (MCADD)
Isovalaeric acidaemia (IVA)
Glutaric aciduria type 1  (GA1)

Question 2

How is MCADD managed ?

Answer 2

with MCAD enzyme deficient you can’t break down fats into ketones for metabolism meaning you rely solely on glucose.

• Never let the child become hypoglycaemic or they die.
• NG tube feeds at night

Question 3

Define specificity ?

Answer 3

The probability that someone without the disease will also test negative.

TN/(FP+TN)

Question 4

Define sensitivity ?

Answer 4

The probability that someone with the disease will correctly test positive

TP/(TP+FN)

Question 5

Define positive predictive value ?

Answer 5

The probability that someone who tests positive actually has the disease.

TP/(TP+FP)

Question 6

Define negative predictive value ?

Answer 6

The probability that someone who tests negative actually does not have the disease.

TN/(TN+FN)

Question 7

types of inheritance

Answer 7

chromosomal 
monogenic (mendelian)
polygenic (mendelian)

Question 8

features of PKU (phenylketonuria)

Answer 8

caused by a phenylalanine hydroxylase deficiency
converts phenylalanine into tyrosine
build up of phenylalanine (toxic) and abnormal metabolites formed
–> phenylpyruvate and phenylacetic acid

Question 9

signs and symptoms of PKU

Answer 9

low IQ
common
investigate - blood phenylalanine level

Question 10

how is PKU treated

Answer 10

monitor diet - enough phenylalanine to keep you going but not enough to be toxic
treatment to be started within first 6 weeks of life

Question 11

what are features fo MCAD deficiency

Answer 11

fatty acid oxidation disorder
cannot produce acetyl coa from the fatty acids
acetyle coa is necessary in the TCA cycle to produce ketones which spares glucose
classic cause of cot death - baby can’t break down fat s- hypoglycaemia and death
measure C6-C10 in screening
tx - ensure the child never becomes hypoglycaemic

Question 12

features of homocysteinuria

Answer 12

lens dislocation
mental retardation
thromboembolism

Question 13

features of CF

Answer 13

failure of CFTR
failure of chloride ions to move from inside the epithelial cells into the lumen
leads to increased absorption of Na+ and water
thick secretions
–> duct obstruction

lungs - recurrent infection
pancreas - malabsorption, steatorrhoea, diabetes
liver - cirrhosis

Question 14

how is CF detected

Answer 14

IRT (immune reactive trypsin)
–> mutation detections
delta F508 most common