Clinical Correlates

Question 1

What is primary lactase deficiency?

Answer 1

• absence of the lactase persistence allele
• cannot produce lactase
• affects ADULTS only
• highest prevalence in northwest Europe

Question 2

What is secondary lactase deficiency?

Answer 2

• deficiency caused by damage to the small intestine as lactase held in the brush border
• occurs in both adults and children
• can be reversed

Question 3

What is congenital lactase deficiency?

Answer 3

• present from birth, infants cannot digest breast milk

- autosomal recessive defect in lactase gene

Question 4

What are the symptoms of lactase deficiency and what is then physical cause?

Answer 4

Symptoms: bloating, cramps, diarrhoea, vomiting

Cause: unable to cleave lactase creates an osmotic pool in the stomach

Question 5

What is normal lactate concentration in plasma?

Answer 5

1mM lactate

Question 6

What is hyperlactaemia?

Answer 6

-lactate levels at 2-5mM

Below renal threshold so can be excreted
No change in plasma pH due to buffers

Question 7

What is lactic acidosis?

Answer 7

Lactate levels above 5mM

Above the renal threshold
Lactate starts appearing in the kidney
pH will lower as buffering systems become saturated

Question 8

What is essential fructosuria?

Answer 8

Missing fructokinase enzyme

Fructose builds up in blood and is excreted in urine

Not clinically worrying

Question 9

What is fructose intolerance?

Answer 9

Missing Aldolase enzyme

Fructose is converted to fructose-1P but then cannot be metabolised further

Fructose-1P can’t be cleaved and builds up in the liver to cause liver damage

Question 10

What 3 enzymes could be absent in galactosemia?

Answer 10

1. Galactokinase
2. Uridyl transferase
3. UDP-galactose epimerase

Question 11

How does galactosemia cause cataract damage?

Answer 11

When galactose cannot be broken down it accumulates and enters different pathways

Galactose is converted to galacticol by the enzyme aldose reductase

Reaction depletes NADPH stores so oxidative damage causes crystalin protein in the eye to form inappropriate disulphide bonds —>forms cataracts

Question 12

What is glucose-6-phosphate dehydrogenase deficiency? (G6PDH)

Answer 12

Without G6PDH the pentose phosphate pathway cannot function and NADPH levels fall and inappropriate disulphide bonds form

• causes cataracts
• forms Heinz bodies in RBC

Question 13

Why is vitamin B1 important in metabolism of carbohydrates?

Answer 13

Pyruvate dehydrogenase (needed for pyruvate —> acetyl coA) needs vitamin B1 to act as a cofactor

Question 14

What is the difference in ketone concentration between physiological ketosis and pathological ketosis?

Answer 14

Physiological = 2-10mM ketone
Pathological = 10mM ketone

Question 15

How do statins lower cholesterol?

Answer 15

They inhibit enzyme HMG CoA reductase to prevent conversion of HMG-coA to cholesterol

Question 16

What is Ehlers-Danlos syndrome and what causes it?

Answer 16

Weakened connective tissue, blood vessels and stretchy skin

Caused by deficiency in Lysyl oxidase (enzyme that forms covalent bonds between tropocollagens) or by mutation in collagen type V

Question 17

When do symptoms of beta thalassaemias appear?

Answer 17

After birth

Question 18

When do symptoms of alpha thalassaemias occur?

Answer 18

Before birth

Question 19

What is Hb Bart’s?

Answer 19

Gamma chains if haemoglobin form tetramers causing alpha and beta chains to precipitate