Inborn errors of metabolism Flashcards
what is an inborn error?
an inherited disorder that affects metabolism
what are IMDs
diseases due to:
- absense, inactivityor reduced activity
of enzymes or other proteins that reguatio metabolic pathways
what was Garrrods Hypothesis of IMDs
A –> A –> C and D
either of these may interfere with the metabolic process
if one thing isnt working properly it can cause levels of a toxic metabolite to build up
classifications of IMDs by affected molecule
carbohydrate amino acid organic acid nucleic acid glycosaminoglycans
classifications of IMDs by cell organelle
lysosomes
mitochondria
peroxisomes
classifications of IMDs by affected pathway
urea cycle glyconeogenesis fatty acid oxdation krebs cycl glycosaminoglycan catabolism
when do IMDs present?
after the neonatal period as an acute, lifethreatening illness
how are IMDs recognised?
clinical symptoms are typically non specific and show up as somethin ele such as sepsis but the parents details are needed tp determine the likeihood of IMD
why is it important to recognise IMDs
- quick treatment to prevent long term damage
- benefit for the next child born
4 broad grops of IMD
- secondaary accumulation of toxins
- enery deprivation
- liver dysfunction with hypoglycaemiae
- dysmorphmism
(overlapping is common)
decribe secondary accumulation of toxins
enzyme converting A to B doesnt work
leads to B decreasing and A accuulating
A is then converted to something else, C which is toxic
clinical presentation of secondary accumulation of toxins
toxins take time to build up in system so can take a while to show
- intoxication, vomiting, coma, liver failure
- acidosis, ketosis
example of secndary accumulation of toxins
propionic acidaemia
enzyme to digest proten missing too much proprionic acid now which is toxic
describe energy deprivation IMD
symtoms due t defciency in the process of energy production or utilisation
ATP levels drop
clinical presentation of energy deprivation
hypoglycamiae and sudden death all metabolic tissues affected - floppiness -lheart failre - circulatory collapse - failure to thrive improvement after energy replacement such as glucose infusion * also seen in adults after time of starvation
example of energy deprivation IMD
MCAD
medium-chain acyl CoA dehydrogenase deficiency
child already with the condition but unknow, fasts for a period of time and the condition now shows up as
prolonged fasting can leads to hypoglyasema and shock because fatty acids are being onvereted properly to energy and thins shut down
describe liver dysfunction/hypoglycaemia IMD
liver essential to maintain glucose levels,
ketones build up leading to actidosis and galactosaemia
what is galactosaemia
liver dysfunction
increased galactose because the enzyme covnerting this isnt working and it accumulates and this can be toxic
what is Hurlers syndrome
a dysmorphism IMD
- accumulation of lysosomes and storage affecting all organs and tissues
whats the role of labs in IMDs
- most will offer a routine set of tests to rule out IMDs
biochem labs do these tests - staff should be educated in the types of IMD
what kind of approach is used for lab investigations of IMD
phase approach
- first line investigations of routinetests
- second line investigation more complex
- confirmatory tests
examples of first line investigations
serum glucose
metabolic acidosis
blood pH
organ function tests
examples of second line investiations
complex looking at several analytes
- plasma urine amino acid
- urine organic acids
