Nitrogen 3

Question 1

What is an inherited metabolic disorder?

Answer 1

Group of genetic diseases involving metabolic defects

Question 2

How can the incidence of IEM be described?

Answer 2

Individually rare but collectively not uncommon

Question 3

What is normally the cause of IEM?

Answer 3

Single gene defects

Question 4

What do IEM usually result in?

Answer 4

Deficiencies of key enzymes

Question 5

What do deficiencies of key enzymes result in?

Answer 5

Abnormal synthesis or catabolism of:

• Proteins
• Amino acids
• Carbohydrates
• Lipids

Question 6

Describe the inheritance of IEM.

Answer 6

• Most show autosomal recessive inheritance

- Heterozygotes are phenotypically normal

Question 7

What are some common clinical features of IEM presenting in childhood?

Answer 7

• Acidosis
• Failure to thrive
• Vomiting, refusal of feeds, irritability
• CNS dysfunction
• Hypoglycaemia
• Unusual odour

Question 8

Where does the urea cycle take place?

Answer 8

It is split between mitochondrial matrix and cytosol

Question 9

What are the 5 enzymes that catalyse the cycle in the liver?

Answer 9

• Carbamoyl phosphate synthetase
• Ornithine transcarbamoylase
• Argininosuccinate sythetase
• Argininosuccinate lyase
• Arginase

Question 10

What is the regulatory enzyme in the urea cycle?

Answer 10

CPS1

Carbamoyl phosphate sythetase

Question 11

What is the allosteric activator of CPS1?

Answer 11

N-acetyleglutamate

Question 12

What is the most common urea cycle defect??

Answer 12

Ornithine transcarbamoylase deficiency

Question 13

What is the genetics behind OTC deficiency?

Answer 13

It is the only X-linked inheritance. The 5 other disorders are autosomal recessive

Question 14

What are the characteristics of OTC deficiency?

Answer 14

• Hyperammonaemia

- Presentation in newborns

Question 15

How do amino acid disorders come about?

Answer 15

• Amino acids can be metabolised into other amino acids, hormones, pigments, neurotransmitters
• Enzymes play a key role
• IEM cause decreased enzyme activity
• Decreased product
• Increased precursors
• Alternative metabolic products

Question 16

What is PKU?

Answer 16

-An autosomal recessive disorder which causes the absence/deficiency of phenylalanine hydroxylase

Question 17

What are the clinical features of PKU?

Answer 17

• Near normal blood Phe at birth
• Rapidly rising Phe levels after feeding commences
• Irritability and feeding difficulties
• Delayed mental development and neurological features
• Musty odour

Question 18

How is PKU diagnosed?

Answer 18

• Guthrie card
• Quantitative amino acid analysis
• Increase blood Phe and decreased blood tyrosine
• Dietary treatment commenced

Question 19

What is the treatment for PKU?

Answer 19

-Low protein diet with protein substitute
-Blood Phe measured
Monitor vitamin and trace elements