Inborn errors of metabolism Flashcards
How many live births are affected by inborn errors of metabolism?
1:1-2000 live births
Inborn errors of metabolism are caused by genetic defects that code for what 3 types of protein (in general)?
1) transport proteins
2) structural proteins
3) enzymes
Why, in inborn errors of metabolism, do you tend not to have complete blockage of a metabollic pathway?
A full blockage in a pathway is unlikely to be compatible with life
Inborn errors of metabolism tend to be caused by reduced function of an enzyme (/structural/transport protein) thus you have a range of severity in each disorder
What kind of genetic defect tends to occur in inborn errors of metabolism?
A mutation which leads to over expression or under expression of a gene, doing something too much or too little is what causes the problems
What is biochemical genetics?
The study/investigation of (primarily) genetic disorders that affect the metabolic pathways of cells
Why do enzymes catalysing reactions give you a degree of control of the rate of reaction?
Can be controlled by over or under expression of genes
In a metabolic pathway involving multiple enzymes, what are the 3 possible damaging consequences of a malfunctioning enzyme towards the end of the pathway?
1) Dont produce enough of the end-point product
2) Intermediates produced prior to that enzyme can accumulate and can themselves be toxic
3) Intermediates that build up prior to that enzyme could be converted to something else which is a toxic substance
How can you work out which enzyme is malfunctioning in a metabolic pathway?
By measuring levels of intermediates and end point products to work out where the blockage occurs
How can vitamin and nutrition deficiencies sometimes mimic inborn errors of metabolism symptoms?
Many enzymes require a co-factor to carry out their function, these are often vitamins, they can give you a biochemical and clinical phenotype similar to the genetic phenotype so you need to work out if there is an actual problem
How can vitamins be useful in treating inborn errors of metabolism?
There is usually some residual enzyme activity there, you can give a vitamin supplement thus providing excess of the cofactor and maximise what is actually there, - this can decrease the symptoms
Give the 3 broad mechanisms of disease of inborn errors of metabolism?
1) Accumulation of a toxin
2) Energy deficiency
3) Deficient production of essential metabolite / structural component
What substance accumulates in patients with urea cycle defects?
Ammonia
Give the 7 clinical effects of acute hyperammonaemia toxicity?
1) Lethargy
2) Poor feeding
3) Vomiting
4) Tachypnoea
5) Convulsions
6) Coma
7) Death
What is porphyria?
Accumulation of porphyrins in the haem synthesis pathway
What is the haem synthesis pathway?
ALA - BPG - Uroporphrin - Corpoporphrin - Protoporphrin - Haem