C - Metabolic Disorders & Screening (E)

Question 1

inherited metaboic disorders result in deficient ____ activity, leading to:
lack of ____
build up of ____
abnormal _____

Answer 1

enzyme
end product
precursors
metabolites

Question 2

what is phenylketonuria

Answer 2

phenylalanine hydrozylase deficiency

Question 3

sx of phenylketonuria

Answer 3

very reduced IQ

Question 4

incidence of PKU

Answer 4

1/5000 - 15,000

Question 5

Ix for PKU

Answer 5

blood phenylalanine (high)

Question 6

tx for PKU
- key thing to remember with timeline of PKU

Answer 6

low phenylalanine diet
- must be started in first 6 weeks of life

Question 7

how is PKU screened for

Answer 7

guthrie card - heel prick

Question 8

CF screening test from guthrie card in lab

Answer 8

high blood immune reactive trypsin

Question 9

how is MCAD screened for

Answer 9

acycl carnatine panel

Question 10

24M confused, resp alkalosis, prolonged clotting and deranged LFTs.
+++ ammonia. Dx?

Answer 10

urea cycle defect

Question 11

what is the urea cycle overall

Answer 11

ammonia –> urea

Question 12

what happens if you have very high ammonia

Answer 12

seizures
coma
death

Question 13

is urea cycle defect recessive or dominant

Answer 13

recessive - one is X linked

Question 14

what other marker is high if you have high ammonia ? why?

Answer 14

glutamine (adding ammonia to glutamate)

Question 15

how do you treat high ammonia

Answer 15

remove ammonia - sodium benzoate / sodium phenylacetate / dialysis
reduce ammonia production - low protein diet

Question 16

flags for urea cycle disorders

Answer 16

vomitting without diarrhoea
respiratory alkalosis
hyperammonaemia
neuroloigcal encephalopathy
avoidance / change in diet (protein)

Question 17

hyperammonaemia with metabolic acidosis & high anion gap

Answer 17

organic acidurias

Question 18

what causes organic acidurias

Answer 18

poor breakdown of branched chain amino acids

Question 19

clinical sign of organic acidurias

Answer 19

cheesy / sweaty smelling urine

Question 20

what compound causes cheesy / sweaty smell of organic acidurias

Answer 20

isovaleryl glycine

Question 21

PC of organic acidurias

Answer 21

unusual odour of urine
lethargy
feeding problems
truncal hypotonia / limb hypertonia
myoclonic jerks
metabolic acidosis with high ammonia
low Ca
neutropaenia, thrombopaenia

Question 22

PC of chronic intermitten form of organic aciduria

Answer 22

recurrent episodes of ketoacidotic coma, cerebral abnormalities

Question 23

name a type of chronic intermitten organic aciduria

Answer 23

Reye’s syndrome

Question 24

Sx of reyes syndrome

Answer 24

vomitting, lethargy, confusion, seizures, resp arrest

Question 25

what triggers reyes syndrome

Answer 25

salicylates, antiemetics, valproate

Question 26

tests for ?reyes

Answer 26

ammonia plasma / urine amino acids urine organic acids plasma / blood glucose and lactate blood spot carnatine profile

Question 27

which test will be abnormal even in remission for reyes

Answer 27

blood spot carnatine profile - all the others need to be done when the Sx are present

Question 28

sugar / ketone level of mitochondrial fatty acid B-oxidation defect (MCAAD)

Answer 28

low sugar low ketones (ketones should be high if sugar low in normal person)

Question 29

signs of MCAAD

Answer 29

hepatomegaly cardiomyopathy

Question 30

lab tests for MCADD

Answer 30

blood ketones urine organic acids blood spot acylcarnitine profile

Question 31

what is galactosaemia

Answer 31

disorder of galactose metabolism (carb breakdown)

Question 32

which galactoseamia form is most common & most severe

Answer 32

gal-1-PUT

Question 33

what effects does galactosaemia have on body

Answer 33

liver and kidney disease

Question 34

PC of galactosaemia

Answer 34

vomitting diarrhoea conjugated hyperbilirubinaemia hepatomegaly hypoglycaemia sepsis - e.coli

Question 35

complication of galactosaemia

Answer 35

galactitiol (bilateral cateracts)

Question 36

what is glycogen storage disease type 1

Answer 36

can't break down glycogen so you end up storing too much of it

Question 37

complications of glycogen storage disease type 1

Answer 37

hepatomegaly nephromegaly hypoglycaemia lactic acidosis neutropaenia

Question 38

why do mitochondrial disorders present at varying ages

Answer 38

heteroplasmy of mitochondrial DNA means a threshold of mutant DNA needs to be reached before Sx show

Question 39

where in the body do mitochondrial disorders affect most

Answer 39

high energy requirement organs - brain, muscle, kidney, retina, endocrine

Question 40

mitochondrial disorders: Sx of Barth syndrome and when does it present

Answer 40

cardiomyopathy, neutropenia, myopathy birth

Question 41

mitochondrial disorders: Sx of MELAS and when does it present

Answer 41

mitochondrial encephalopathy, lactic acidosis, stroke like episodes 5-15

Question 42

mitochondrial disorders: Sx of kearns-sayre and when does it present

Answer 42

opthalmoplegia, retinopathy, deafness, ataxia 12-30

Question 43

Ix of mitochondrial disorders

Answer 43

elevated lactate (esp after periods of fasting) CSF lactate / pyruvate CSF protein CK / muscle biopsy mitochondrial DNA analysis