Lecture 30: Inborn errors of metabolism (IEMs) Flashcards
What are inborn errors of metabolism?
genetic conditions in which an individual lacks an enzyme that controls a specific metabolic pathway
What are the two general effects of an enzyme deficiency?
1) accumulation of substrate behind the block in the pathway
2) lack of substrate production ahead of the block in the pathway
How often do IEMs occur?
Approx 1:1-2,000 live births
What is the clinical significance of side reactions produced by an accumulation of substrates behind blocks in enzyme pathways?
the new compounds can be used to diagnose inborn errors of metabolism
What is the name given to non-protein ‘helper’ molecules that aid enzyme catalysed transformations?
Cofactors
Give the three mechanisms of disease associated with inborn errors of metabolism:
1) accumulation of a toxin
2) energy deficiency
3) deficient production of essential metabolites or structural components
True or false: hyperammonaemia is a medical emergency
True
What causes hyperammonaemia?
urea cycle defects
What is the role of the urea cycle?
to convert toxic ammonia formed from amino acid deamination to urea for excretion
What is the firm step in the urea cycle?
ammonia is combined with carbon dioxide to form carbamoyl phosphate
What effect does an upper pathway urea cycle enzyme deficiency have on the onset of hyperammonaemia?
faster onset
Give two upper pathway urea cycle enzymes:
1) CPS1
2) NAGS
Give two lower pathway urea cycle enzymes:
1) arginase
2) agiosuccinic synthase
What effect does a lower pathway urea cycle enzyme deficiency have on the onset of hyperammonaemia?
Slower onset
Give 8 clinical effects of acute hyperammonaemia:
1) lethargy
2) poor feeding
3) convulsions
4) vomiting
5) encephalopathy
6) tachypnoea
7) coma
8) death
The disruption of which metabolic pathway results in the accumulation of porphyrins?
haem production
What does the outcome of hyperammonaemia depend on?
- Extent of hyperammonaemia ( NH3 concentration)
- Duration of elevation
Give the 6 molecules produced at each stage of haem production metabolism:
1) ALA
2) PBG
3) uroporphyrin
4) coproporphyrin
5) protoporphyrin
6) haem
True or false: the build up of porphyrins has toxic effects
True
The build up of which two porphyrins causes acute porphyria?
1) ALA
2) PBG
Give 6 symptoms of acute porphyria:
1) abdominal pain
2) vomiting and diarrhoea
3) insomnia
4) seizures
5) palpitations
6) red/ brown urine
The accumulation of which three porphyrins causes photosensitive porphyria?
1) uroporphyrin
2) coproporphyrin
3) protoporphyrin
How does the accumulation of photosensitive porphyrins cause disease?
they are stimulated by light to produce heat
Give 5 symptoms of photosensitive porphyria:
1) sensitivity to the sun
2) increased hair growth
3) fragile skin
4) blisters that take weeks to heal
5) red/ brown urine
