Metabolic disorders Flashcards
How are metabolic disorders detected on newborn screening?
Guthrie blood spot test at 6 days age
What does the guthrie blood spot test testing for? (5)
- phenylketonuria
- congenital hypothyroidism
- cystic fibrosis
- sickle cell disease
- medium chain acylCoA deficiency
What is phenylketonuria?
Phenylanine hydroxylase deficiency
What is cystic fibrosis?
Mutation in CFTR (F508del most common)
viscous secretions causing ductal blockages
How to screen for cystic fibrosis?
Immune reactive trypsin
if positive -> DNA mutation detection
What is Medium chain AcylCoA dehydrogenase deficiency?
Fatty acid oxidation disorder
How to screen for Medium chain AcylCoA dehydrogenase deficiency?
Acylcarnitine levels by tanden mass spectrometry
When talking about specificity and sensitivity is this regarding the population or the test itself?
The population
When talking about positive and negative predictive values are we talking about the population or the test?
The test itself
What is specificity?
The probability that someone without the disease will correctly test negative
How to calculate specificity?
TN / (FP + TN)
e.g. 85 people without CF, 80 actually test negative.
-> 80/85 = 94%
What is sensitivity?
Probability that someone with the disease will correctly test positive
How to calculate sensitivity?
TP/ (TN+FN)
e.g. 100 people with CF and 90 test positive that have the disease
-> 90/100 = 90%
What is the positive predictive value?
How is it calculated
PPV is the probability that someone who tests positive actually has the disease
TP / (TP +FP)
e.g. 95 people tested positive of which 90 had the disease
-> 90/95 = 95%
What is the negative predictive value?
How is it calculated
NPV is the probability that someone who tests negative actually has the disease
TN / (TN +FN)
e.g. 90 people tested negative of which 90 didn’t have the disease
-> 80/90 = 89%
What group 1 (Accumulation of toxins) metabolic disorders exist?
Organic acidaemias ‘Acidurias)
Urea cycle disorders (10 total)
Phenylketonuria
Homocystinuria
Tyrosinaemia
What are organic acidaemias?
You see Hyperammoniaemia + metabolic acidosis + high AG + high ketones
Associated with unusual odour in urine
Causes toxic encephalopathy
What is the test for organic acidaemias?
Plasma ammonia, plasma amino acids,
There are two types of organic acidaemias to remember
What are they and a distinct feature of both
Isovaleric acidaemia = cheesy /sweaty urine smell
Maple syrup urine disease = sweet odour to urine, sweaty feet
What inheritance pattern do urea cycle disorders follow?
All are autosomal recessive
1 is X linked. (OTC deficiency)
What are the key features of urea cycle deficiency presentation?
Hyperammoniaemia = encephalopathy
In a child : hyperammonaemia state after party having eaten alot of meat
In a adult : Hx psychiatric illness / ADHD
How to manage urea cycle disorders?
Remove excess ammonia via dialysis / sodium benzoate
long term = low protein diet
How to test for urea cycle disorders?
Test = blood ammonia (from a free flowing sample, kept in ice and rushed to laboratory) = HIGH
○ Other tests = glutamine levels (HIGH), urine orotic acid (HIGH)
What causes phenylketonuria?
Deficiency of phenylalanine hydroxylase
= high levels of toxic phenylalanine -> build up on phenulpyruvate + phenylacetic
