C - Metabolic Disorders & Screening (E) Flashcards
inherited metaboic disorders result in deficient ____ activity, leading to:
lack of ____
build up of ____
abnormal _____
enzyme
end product
precursors
metabolites
what is phenylketonuria
phenylalanine hydrozylase deficiency
sx of phenylketonuria
very reduced IQ
incidence of PKU
1/5000 - 15,000
Ix for PKU
blood phenylalanine (high)
tx for PKU
- key thing to remember with timeline of PKU
low phenylalanine diet
- must be started in first 6 weeks of life
how is PKU screened for
guthrie card - heel prick
CF screening test from guthrie card in lab
high blood immune reactive trypsin
how is MCAD screened for
acycl carnatine panel
24M confused, resp alkalosis, prolonged clotting and deranged LFTs.
+++ ammonia. Dx?
urea cycle defect
what is the urea cycle overall
ammonia –> urea
what happens if you have very high ammonia
seizures
coma
death
is urea cycle defect recessive or dominant
recessive - one is X linked
what other marker is high if you have high ammonia ? why?
glutamine (adding ammonia to glutamate)
how do you treat high ammonia
remove ammonia - sodium benzoate / sodium phenylacetate / dialysis
reduce ammonia production - low protein diet
flags for urea cycle disorders
vomitting without diarrhoea
respiratory alkalosis
hyperammonaemia
neuroloigcal encephalopathy
avoidance / change in diet (protein)
hyperammonaemia with metabolic acidosis & high anion gap
organic acidurias
what causes organic acidurias
poor breakdown of branched chain amino acids
clinical sign of organic acidurias
cheesy / sweaty smelling urine
what compound causes cheesy / sweaty smell of organic acidurias
isovaleryl glycine
PC of organic acidurias
unusual odour of urine
lethargy
feeding problems
truncal hypotonia / limb hypertonia
myoclonic jerks
metabolic acidosis with high ammonia
low Ca
neutropaenia, thrombopaenia
PC of chronic intermitten form of organic aciduria
recurrent episodes of ketoacidotic coma, cerebral abnormalities
name a type of chronic intermitten organic aciduria
Reye’s syndrome
Sx of reyes syndrome
vomitting, lethargy, confusion, seizures, resp arrest
what triggers reyes syndrome
salicylates, antiemetics, valproate
tests for ?reyes
ammonia
plasma / urine amino acids
urine organic acids
plasma / blood glucose and lactate
blood spot carnatine profile
which test will be abnormal even in remission for reyes
blood spot carnatine profile
- all the others need to be done when the Sx are present
sugar / ketone level of mitochondrial fatty acid B-oxidation defect (MCAAD)
low sugar
low ketones
(ketones should be high if sugar low in normal person)
signs of MCAAD
hepatomegaly
cardiomyopathy
lab tests for MCADD
blood ketones
urine organic acids
blood spot acylcarnitine profile
what is galactosaemia
disorder of galactose metabolism (carb breakdown)
which galactoseamia form is most common & most severe
gal-1-PUT
what effects does galactosaemia have on body
liver and kidney disease
PC of galactosaemia
vomitting
diarrhoea
conjugated hyperbilirubinaemia
hepatomegaly
hypoglycaemia
sepsis - e.coli
complication of galactosaemia
galactitiol (bilateral cateracts)
what is glycogen storage disease type 1
can’t break down glycogen so you end up storing too much of it
complications of glycogen storage disease type 1
hepatomegaly
nephromegaly
hypoglycaemia
lactic acidosis
neutropaenia
why do mitochondrial disorders present at varying ages
heteroplasmy of mitochondrial DNA means a threshold of mutant DNA needs to be reached before Sx show
where in the body do mitochondrial disorders affect most
high energy requirement organs - brain, muscle, kidney, retina, endocrine
mitochondrial disorders:
Sx of Barth syndrome and when does it present
cardiomyopathy, neutropenia, myopathy
birth
mitochondrial disorders:
Sx of MELAS and when does it present
mitochondrial encephalopathy, lactic acidosis, stroke like episodes
5-15
mitochondrial disorders:
Sx of kearns-sayre and when does it present
opthalmoplegia, retinopathy, deafness, ataxia
12-30
Ix of mitochondrial disorders
elevated lactate (esp after periods of fasting)
CSF lactate / pyruvate
CSF protein
CK / muscle biopsy
mitochondrial DNA analysis
