metabolic disorders and screening 2 Flashcards
how do you take an ammonia sample
Free flowing sample,
to lab stat on ice
how many enzymes are in the urea cycle
7
what is a urea cycle defect
deficiency in any of the urea cycle enzymes and 3 others (Lysinuric protein intolerance, HHH, Citrullinaemia type II)
-> hyperammonaemia
inheritence of urea cycle defects
recessive
except Ornithine transcarbamylase deficiency (OTC) which is X-linked
problem with urea cycle defect
Urea cycle starts with ammonia and finishes with urea
Ammonia is V toxic
One day in hyperammonaemic coma – lost all IQ
Coma >300Umol/L
problem with urea cycle defect
Urea cycle starts with ammonia and finishes with urea
Ammonia is V toxic
One day in hyperammonaemic coma – lost all IQ
Coma >300Umol/L
what should you do when you find high ammonia
Send sample to lab to 2nd testing centre – measure other markers of urea cycle disorder
Cant excrete that amount of ammonia
So add ammonium group to glutamate -> glutamine -> plasma glutamine is high
Amino acids in cycle are either high/absent
Turn around time is 5days.
Urine orotic acid is also measured
rx of urea cycle defect
Remove ammonia
* sodium benzoate,
* or sodium phenylacetate
Reduce ammonia production – low protein diet
ABG sign of hyperammonaemia
resp alkalosis
note this is rare and is a sign of poisoning and hyperammonaemia
presentation of hyperammonaemia
long term psychiatric condition
illness after large protein intake
what are the indicators of urea cycle disorder
vomiting w/o diarrhoea
resp alkalosis
hyperammonaemia
avoidance change in diet
neurological encephalopathy w/o encephalitis
summarise isovaleric acidaemia
hyperammonaemia with metabolic acidosis and high anion gap:
Break down leucine –** take of ammonia group** with transaminases
Break down product of leucine is isovaleryl CoA
If next enzyme is absent
Get isovaleric acidaemia
Try and offload toxic metabolites
Cant transport anything with high energy group across membrane
Associated with funny smelling urine – maple syrup smelling urine disease (3OH-isovaleric acid isovaleryl glycine)
presentation of organic acidurias in neonates
unusual odour
lethargy,
feeding problems,
truncal hypotonia / limb hypertonia,
myoclonic jerks
hyperammonaemia with metabolic acidosis and high anion gap
hypoca
neutropenia
thrombopenia
pancytopenia
presentation of chronic intermittent organic acidurias
Recurrent episodes of ketoacidotic coma,
cerebral abnormalities,
Reye syndrome
* Vomiting,
* lethargy,
* increasing confusion,
* seizures,
* decerebration,
* respiratory arrest
Triggered by: e.g. salicylates, antiemetics, valproate
Reye syndrome metabolic screen
collect in acute episode:
* blood ammonia
* plasma/urine amino acid
* urine organic acids
* blood glucose and lactate
abnormal in remission
* blood spot carnitine profile - Intracellular build up of metabolites – export as carnitine – can be picked up on blood profile
chemistry of MCADD
mitochondrial fatty acid B oxidation deficiency
hypoketotic hypoglycaemia
hepatomegaly and cardiomyopathy
bloods:
* blood ketones
* urine organic acids
* blood spot acylcarnitine profile
why do you get hypoketotic hypoglycaemia in MCADD
If hypoglycaemic – should be making ketones and should have ketones in urine
If not making ketones – then show cant break down fats
what is galactose-1-phoshate uridyl transferase (Gal-1-PUT) disorder
it is a galactosaemia
it is the most common and severe galactose metabolism disorder
get build up of gal-1-phosphate which
-> liver and kidney disease
do we screen for galactose-1-phoshate uridyl transferase (Gal-1-PUT)
no - will present before get screening result
presentation of galactose-1-phoshate uridyl transferase (Gal-1-PUT)
vomiting
diarhoea
cBR
hepatomegaly
hypoglycaemia
bilateral cataracts
Develop e coli sepsis – gal-1-phosphate inhibits immune responses
how do you get cataracts in galactose-1-phoshate uridyl transferase (Gal-1-PUT) deficiency
gal-1-phosphate becomes substrate for aldolase in eye -> galacititiol
-> bilateral cataracts
ix and mx of galactose-1-phoshate uridyl transferase (Gal-1-PUT) deficiency
Urine reducing substances - would get high galactose
Red cell Gal-1-PUT
Rx:
* Galactose isn’t essential – so just cnat have milk
