metabolic disorders 2 Flashcards
which Inherited metabolic disorders typocally present like:
Cerebral oedema, seizures, comatose
Disorders of the urea cycle leading to :
Hyperammonaemia
disorders include:
○ Lysinuric protein intolerance
○ Hyperornithinaemia-Hyperammonemia-Homocitrullinuria (HHH)
○ Citrullinaemia type II
○ Ornithine transcarbamylase deficiency (OTC)
how are the disorders of the urea cycle inherited?
Autosomal recessive
except ○Ornithine transcarbamylase deficiency (OTC) -> X linked inheritance
what will ivx show in testing for disorders of urea cycle?
amino acids - high or absent
urine orotic acid
rx:
remove ammonia - give sodium benzoate or phenylacetate or dialysis
reduce ammonia production
urea cycle disorders present how?
Long term psychiatric disorders - eg ADHD
avoidance of protein, subsequent illness around family celebrations eg Christmas
confusion, disorientation, nausea, vomintg etc
○ Vomiting without diarrhoea ○ Respiratory alkalosis ○ Hyperammonaemia ○ Neurological encephalopathy ○ Avoidance or change in diet
Hyperammonaemia with Metabolic ACIDOSIS and High Anion Gap is associated with?
organic acidurias ->
The most important involve the defects within the complex metabolism of the branched chain amino acids (leucine, isoleucine and valine)
isovaleric academia (organic acidurias) present how? and why?
- Unusual odour or funny smelling urine due to:
3OH-isovaleric acid - cheesy/sweaty smell
isovaleryl glycine - lethargy, feeding problems
- truncal hypotonia
- limb hypertonia
- myoclonic jerks
ivx findings;
hypocalcaemia, neutropaenia, thrombocytopaenia, pancytopaenia
§ Hyperammonaemia with a metabolic acidosis and a high anion gap (not lactate)
name a Chronic Intermittent Form of organic aciduria, how it presents and its triggers?
REYE SYNDROME
□ Vomiting □ Lethargy □ Increased confusion □ Seizures □ Decerebration □ Respiratory arrest
□ Triggered by: salicylates (aspirin), anti-emetics, valproate
why is aspirin/salicylate not given to children anymore?
triggers reye’s syndrome
what do we screen for in reye’s syndrome?
○ Plasma ammonia ○ Plasma/urine amino acid ○ Urine organic acids ○ Plasma glucose and lactate ○ Blood spot carnitine profile (stays abnormal in remission)
○ NOTE: the top 4 should be collected during the acute episode because the abnormal metabolites will disappear after a few days
you note hypoketotic hypoglycaemia (+ hepatomegaly and cardiomyopathy). what are you thinking?
Mitochondrial Fatty Acid Beta-Oxidation Defects
how do we investigate Mitochondrial Fatty Acid Beta-Oxidation Defects?
○ Blood ketones
○ Urine organic acids
○ Blood spot acylcarnitine profile
§ Conjugated hyperbilirubinaemia is always ___?
pathological
list the types of Galactosaemia. what is galactosaemia?
disorders of carbohydrate breakdown
Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency
how do Galactosaemias present?
§ Vomiting
§ Diarrhoea
§ Hepatomegaly
§ Hypoglycaemia
very important:
§ Conjugated hyperbilirubinaemia
§ Sepsis (because galactose-1-phosphate inhibits immune responses)
-> bilateral catarcts - due to aldolase in eyes lenses
ivx for galactosaemia’s?
treatment?
§ Urine reducing substances (high levels of galactose)
§ Red cell Gal-1-PUT
treatment:
§ Avoid galactose (e.g. milk)
