Chemical Pathology 5 - Metabolic disorders and screening

Question 1

Deficiency of which enzyme causes phenylketouria?

Answer 1

Phenylalanine hydroxylase

Question 2

What builds up in PKU that causes toxicity?

Answer 2

Tyrosine

Question 3

What number must you use when requesting a metabolic screen?

Answer 3

OMIM number

Question 4

What will be the result of not treating PKU shortly after birth?

Answer 4

IQ <50

Question 5

How is PKU diagnosed?

Answer 5

Based on blood phenylalanine level, as >400 different mutations can cause PKU!

Question 6

How quickly does PKU treatment need to be initiated in order to be effective?

Answer 6

First 6 weeks of life

Question 7

What is the test for cystic fibrosis in the neonate?

Answer 7

High immune reactive trypsin

Question 8

What is MCADD?

Answer 8

Enzyme deficiency that prevents production of acetyl CoA, which permits glucose sparing
Therefore, if you can’t break down fat, you may die of hypoglycaemia

Question 9

What metabolic defect can cause hyperammonaemia?

Answer 9

Urea cycle defect

Question 10

How can hyperammonaemia be treated?

Answer 10

Remove ammonia via sodium benzoate or sodium phenyl acetate

Reduce ammonia production (low protein diet)

Question 11

What is the typical triad of signs for organic aciduria?

Answer 11

Hyperammonaemia
Metabolic acidosis
High anion gap

Question 12

What unusual odour might be smelt on a patient with isovaleric acidaemia?

Answer 12

Cheesy and sweaty

need to use ice when you are sweaty; and cheese makes everything better

Question 13

What are the typical neurological findings in organic acidurias?

Answer 13

Truncal hypotonia and limb hypertonia

Question 14

What condition causes chronic intermittent organic aciduria?

Answer 14

Reye syndrome

Question 15

Recall 3 drugs that can precipitate symptoms in Reye syndrome

Answer 15

Salicylates
Anti-emetics
Valporate

Question 16

What specialist test should be done in cases of hyperammonaemia?

Answer 16

Blood spot carnitine profile

Question 17

Which inherited metabolic disorder causes a hypoketotic hypoglycaemia?

Answer 17

MCADD

Question 18

What is the most common disorder of carbohydrate metabolism?

Answer 18

Gal-1-put

aka galactossaemia

Question 19

How should Gal-1-Put be treated?

Answer 19

Abstain from drinking milk

Question 20

What may be the consequence of not identifying MCADD in infancy?

Answer 20

Bilateral cataracts

Question 21

Recall 3 signs of glycogen storage disease type 1

Answer 21

enzyme that breaks down G6P –> glucose is lacking (glucose 6 phosphatase deficiency)

Hypoglycaemia
Neutropaenia
Lactic acidosis

hepatomegaly+nephromegaly

Question 22

How does Gal-1-Put present in neonates?

Answer 22

Diarrhoea
Vomiting
Conjugated bilirubinaemia

Question 23

When, and in which organ, do mitochondrial disorders present?

Answer 23

At any age in any organ!

Question 24

Recall 3 mitochondrial disorders

Answer 24

BARTH syndrome
MELAS
Kearns Sayre syndrome

Question 25

What abnormal blood results would be suggestive of a mitochondrial disorder?

Answer 25

Elevated lactate, even when fasted

Unexplained raised CK

Question 26

What is the typical histological finding in mitochondrial disorders?

Answer 26

Ragged red fibres