Chem path 5s - Metabolic disorders 1

Question 1

What is the most common pattern of metabolic disease inheritance?

Answer 1

Autosomal

Question 2

What are the three types of inherited disorders?

Answer 2

Chromosomal, polygenic, monogenic

Question 3

deficient enzyme activity can lead to biochemical hallmarks of the metabolic disorder. What are these?

Answer 3

Lack of end product
Build up of pre-cursors
Abnormal, often toxic metabolites (due to large amount of substrate that does not usually react with the enzyme, start reacting)

Question 4

What is the deficiency in phenylketonuria?

Answer 4

Phenylalanine hydroxylase

Question 5

What does phenylalanine hydroxylase do?

Answer 5

Converts phenylalanine in to tyrosine

Question 6

If deficient in PAH, what biocehmical changes are seen?

Answer 6

Build up of phenylalanine (toxic)

Abnormal metabolites: phenylpyruvate and phenylacetic acid

Question 7

Where is phenylacetic acid detected?

Answer 7

In the urine

Question 8

What is the prevalence of pKU?

Answer 8

1 in 5,000 (common)

Question 9

What are the key features of PKU?

Answer 9

Low IQ (<50)
Musty odour
Behavioural issues

Question 10

What is the test for PKU?

Answer 10

Check serum for phenylalanine

Question 11

What is the management of PKU?

Answer 11

Phenylalanine dietary restriction, management has to be started within the FIRST 6-WEEKS OF LIFE

Question 12

What is sensitivity?

Answer 12

The number of true positives/ total number with the disease (Fraction)

Question 13

What is specificity?

Answer 13

The true negatives / total number without the disease

Question 14

What is +ve predictive value?

Answer 14

True positives/ total number with positive RESULT

Question 15

What is -ve predictive value?

Answer 15

True negatives / total number with negative RESULT

Question 16

What tends to be prioritised in IMDs?

Answer 16

sensitivity as do NOT want to miss a diagnosis

Question 17

When is the Guthrie screen performed?

Answer 17

Days 5-8 of life

Question 18

On the Guthrie card, what is the diagnosis of congenital hypothyroidism based on?

Answer 18

High TSH

Question 19

How many classes of cystic fibrosis are there?

Answer 19

6

Question 20

What is CF caused by?

Answer 20

Failure of the cystic fibrosis transmembrane conductance regulator (CFTR) which leads to the inability of chloride ions in the epithelial cells to move out in to the lumen, increased Na+/Water reabsorption –> viscous secretions –> duct blockage

Question 21

What is the screening test for CF?

Answer 21

High immune reactive trypsinogen (IRT)

Question 22

What is the most common CF mutation?

Answer 22

DF508

Question 23

How do you interpret CF screening (IRT) results?

Answer 23

If the IRT >99.5th centile in 3 blood spots –> mutation detections
There are 4 very common mutations. If you get 2/4 mutations then a diagnosis of CF is confirmed. If you get 1/4 mutations, the panel is extended to 28 mutations. If youget 0/4 mutations, you do another IRT at 21-28 days.

Question 24

What kind of disorder is MCADD?

Answer 24

Fatty acid oxidation disorder

Question 25

If you are deficient in MCAD, what will happen?

Answer 25

No production of acetyl-CoA from fatty acids. Acetyl-CoA is used in the TCA cycle to produce ketones, which spares glucose (brain dependent on glucose metabolism) . You use fat when you are fasting or between meals, in order to spare your glucose stores.

Question 26

What does MCADD classically cause in infants?

Answer 26

Cot death. If a baby cannot break down fats then when they are not feeding they will get massively hypoglycaemic and die.

Question 27

How is MCADD screened for?

Answer 27

Measuring C6-C10 acylcarnitine using tanden mass spectrometry

Question 28

How do you treat MCADD?

Answer 28

make sure the child NEVER becomes hypoglycaemic, and hence never becomes reliant on fats for energy

Question 29

What is the defect in homocystinuria?

Answer 29

There is a failure of remethylation of homocysteine

Question 30

What are the clinical features of homocystinuria?

Answer 30

Lens dislocation Mental retardation Thromboembolism Brittle hair/ fair skin

Question 31

Which nine disorders are currently screened for using the Guthrie screen?

Answer 31

``` PKU Congenital hypothyroidism CF MCADD SCD Maple syrup urine disease Isovaleric acidaemia Glutaric aciduria type I LCADD ```