metabolic disorders and screening 2

Question 1

how do you take an ammonia sample

Answer 1

Free flowing sample,
to lab stat on ice

Question 2

how many enzymes are in the urea cycle

Answer 2

7

Question 3

what is a urea cycle defect

Answer 3

deficiency in any of the urea cycle enzymes and 3 others (Lysinuric protein intolerance, HHH, Citrullinaemia type II)

-> hyperammonaemia

Question 4

inheritence of urea cycle defects

Answer 4

recessive

except Ornithine transcarbamylase deficiency (OTC) which is X-linked

Question 5

problem with urea cycle defect

Answer 5

Urea cycle starts with ammonia and finishes with urea
Ammonia is V toxic
One day in hyperammonaemic coma – lost all IQ
Coma >300Umol/L

Question 6

problem with urea cycle defect

Answer 6

Urea cycle starts with ammonia and finishes with urea
Ammonia is V toxic
One day in hyperammonaemic coma – lost all IQ
Coma >300Umol/L

Question 7

what should you do when you find high ammonia

Answer 7

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

Question 8

rx of urea cycle defect

Answer 8

Remove ammonia
* sodium benzoate,
* or sodium phenylacetate

Reduce ammonia production – low protein diet

Question 9

ABG sign of hyperammonaemia

Answer 9

resp alkalosis

note this is rare and is a sign of poisoning and hyperammonaemia

Question 10

presentation of hyperammonaemia

Answer 10

long term psychiatric condition

illness after large protein intake

Question 11

what are the indicators of urea cycle disorder

Answer 11

vomiting w/o diarrhoea
resp alkalosis
hyperammonaemia
avoidance change in diet
neurological encephalopathy w/o encephalitis

Question 12

summarise isovaleric acidaemia

Answer 12

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)

Question 13

presentation of organic acidurias in neonates

Answer 13

unusual odour
lethargy,
feeding problems,
truncal hypotonia / limb hypertonia,
myoclonic jerks
hyperammonaemia with metabolic acidosis and high anion gap
hypoca
neutropenia
thrombopenia
pancytopenia

Question 14

presentation of chronic intermittent organic acidurias

Answer 14

Recurrent episodes of ketoacidotic coma,
cerebral abnormalities,
Reye syndrome
* Vomiting,
* lethargy,
* increasing confusion,
* seizures,
* decerebration,
* respiratory arrest

Triggered by: e.g. salicylates, antiemetics, valproate

Question 15

Reye syndrome metabolic screen

Answer 15

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

Question 16

chemistry of MCADD

Answer 16

mitochondrial fatty acid B oxidation deficiency

hypoketotic hypoglycaemia
hepatomegaly and cardiomyopathy

bloods:
* blood ketones
* urine organic acids
* blood spot acylcarnitine profile

Question 17

why do you get hypoketotic hypoglycaemia in MCADD

Answer 17

If hypoglycaemic – should be making ketones and should have ketones in urine

If not making ketones – then show cant break down fats

Question 18

what is galactose-1-phoshate uridyl transferase (Gal-1-PUT) disorder

Answer 18

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

Question 19

do we screen for galactose-1-phoshate uridyl transferase (Gal-1-PUT)

Answer 19

no - will present before get screening result

Question 20

presentation of galactose-1-phoshate uridyl transferase (Gal-1-PUT)

Answer 20

vomiting
diarhoea
cBR
hepatomegaly
hypoglycaemia
bilateral cataracts
Develop e coli sepsis – gal-1-phosphate inhibits immune responses

Question 21

how do you get cataracts in galactose-1-phoshate uridyl transferase (Gal-1-PUT) deficiency

Answer 21

gal-1-phosphate becomes substrate for aldolase in eye -> galacititiol
-> bilateral cataracts

Question 22

ix and mx of galactose-1-phoshate uridyl transferase (Gal-1-PUT) deficiency

Answer 22

Urine reducing substances - would get high galactose
Red cell Gal-1-PUT

Rx:
* Galactose isn’t essential – so just cnat have milk