26- Clinical Biochemistry- Inherited metabolic disease

Question 1

Describe the principles of how inherited metabolic diseases occur

Answer 1

Genetic condition
Result in enzyme deficiency
Accumulation of metabolic products in urine blood or other tissues

Question 2

What are examples of acute presentations?

Answer 2

Vomiting 
Lethargy
Poor feeding 
Metabolic Acidosis 
Hypoglycaemica
Seizures

Question 3

What are examples of chronic presentations?

Answer 3

Failure to thrive 
Development delay 
Organomegaly
Seizures / neuromuscular signs 
Eye changes

Question 4

What are examples of inherited metabolic diseases?

Answer 4

Phenylketonuria
Medium Chain Acyl CoA Dehydrogenase Deficiency
Urea Cycle defects
Homocystinuria

Question 5

What are symptoms of PKU?

Answer 5

Fair skin and hair 
Intellectual impairment 
Epilepsy 
Movement Disorder
Autistic Behaviour 
Eczema

Question 6

What is the mode of inheritance for PKU?

Answer 6

Autosomal recessive

Question 7

What food are restricted in a diet for PKU?

Answer 7

Meat and fish
Diary
Nuts
Asaprtame

Question 8

What happens when there is excess substrate that is toxic?

Answer 8

Leads to deficient enzyme and toxic metabolites produced

This means there will be absence or deficiency of product

Question 9

How is Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD) managed?

Answer 9

Avoid prolonged fasting 
CHO before bed 
Breakfast on time 
Emergency regime 
Advice regarding alcohol intake

Question 10

What are signs of urea cycle defects?

Answer 10

Very high ammonia levels
Often mild alkalosis
Plasma amino acids- may be high glutamine, low arginine
Urine- orotic acid present

Question 11

What are the consequences of hyperammonaemia?

Answer 11

Mainly CNS

NH3 converted to glutamine which leads to cerebral odema

Question 12

How do you manage hyperammonaemia?

Answer 12

Reduce prouction of ammonia by protein restricted diet and adequate calorie intake

Increase renal excretion of ammonia

Question 13

What causes homocystinuria?

Answer 13

Deficiency of cysthione- beta-synthase

Accuumulation of homocysteine and metionine

Question 14

What parts of the body is affected by homocytinuria?

Answer 14

Eyes
Brain
Skeleton
Blood vessels

Question 15

What treatment is given to patients with homocystinuria?

Answer 15

Trial of vtitamin B6
Restrict "natural" protein 
Ensure adequate protein intake
Supplement folic acid and B12
Betaine