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what is the epidemiology of inborn errors of metabolism?

they are individually rare but collectively significant. They occur roughly 1 in 1-2000 live births and in Yorkshire alone there are around 25-50 cases p.a. Most will present in childhood but with advances in treatments and diagnostics and milder phenotypes there are some in adulthood.


why are they sometimes not diagnosed?

they are the last things that doctors think of as they are so rare and symptoms can overlap with common conditions


what are three products that glutamate can make?

glutamine, carbomyl P and glutamyl P


what is carbomyl P used for?

when with ornithine it can make citrulline which then makes arginino succinate, then arginine and then back to ornithine by giving off urea


other that citrulline, what else can ornithine make?

glutamine semialdehyde


what else can produce glutamine semialdehyde?

glutamyl P


on a gene, out of the operator repressor and structural regions, a mutation in which part will affect proteins?

in the structural part. The protein can then make enzymes, be used for structures or transport.


how is the urea cycle affected by mutation?

in the urea cycle ammonia is converted to non toxic urea. Mutations can affect any step of this cycle


what are disorders commonly a result of and how does this affect cells?

a lot are enzyme defects - affects the biochemical reactions occurring in cells


what can affect how transporters move substances across membranes?

a lysosomal storage disorder


what happens if a mutation in a protein coding gene is subtle?

will only slightly change the structure and therefore proteins are functional but a reaction may occur slowly


what affects how much of a protein is being produced?

where the mutation is located - if it is in the regulatory regions of the gene - this means that the protein can be under or overproduced


why may some mutations not be seen?

some mutations are in genes that are so essential that they are not compatible with life


how can accumulation lead to a disorder?

a substrate may be fine at low levels but become toxic once it has accumulated due to lack of enzyme converting it and therefore once it has crossed the threshold value is toxic


how can new toxic products be made from a deficiency in an enzyme further along a metabolic pathway?

there is accumulation of previous substrates which can then bind unspecifically and make new compounds which may be toxic


how can you identify the mutation or deficiency?

you can identify and measure the new compounds made to see what is accumulating


what is biochemical genetics?

it is the study or investigation of primarily genetic disorders that affects the metabolic pathways of cells


what is a cofactor?

it is a vitamin or micronutrient that is needed to be bound to an enzyme for it to work properly - enzymes need it to work properly


how can a vitamin deficiency result in pathway defects?

they can give a secondary defect


how can vitamins be used as treatments?

they will stimulate enzymatic activity


what are three mechanisms of disease?

accumulation of a toxin, energy deficiency or deficient production of essential metabolite/structural component


what results in urea cycle defects?

ammonia accumulation - hyperammonaemia toxicity


what are clinical features of hyperammonaemia?

lethargy, poor feeding, vomiting, tachypnoea, convulsions, coma, death


what is the main function of of the urea cycle?

to detoxify ammonia - too much is a medical emergency


why does it take a few days after birth for the hyperammonaemia to be recognised?

there is a latent period as it takes a few days for cycle to start working and then a few days for accumulation


what is the management of of hyperammonaemia?

can stop the catabolic pathways and make the patient anabolic - need to reduce the level of ammonia in the blood and protein restriction to keep levels of ammonia down


summarise the urea cycle?

HCO3 and NH3 combine to make carbamoyl phosphate. This then combines with ornithine to make citrullin and then eventually urea. Carbomyl P also make pyrimidines


what is porphyria?

it is a group of disorders that result from a build up of natural chemicals that make porphyrin which is essential for the function of Hb


what are the possible signs of acute porphyria?

abdo, chest, back or leg pain, insomnia, high blood pressure, diarrhoea and vomiting, palpitations, muscle weakness, tingling, paralysis or pain, seizures, red or brown urine, convulsions, mental changes, breathing problems and anxiety


what are signs of photosensitive porphyria?

sensitivity to sun or artificial light, blistering and ages to heal, sudden painful erythema and oedema, itching, fragile skin, increased hair growth, red brown urine