Chem path 6s - Metabolic disorders 2 Flashcards
What are two key features of urea cycle disorders?
Hyperammonia and respiratory alkalosis
What mode of inheritance do urea cycle disorders tend to have?
Autosomal recessive, hence there isn’t often a family history
Which urea cycle disorder does NOT have an AR inheritnece?
Ornithine transcarbamylase deficiency - it is X-linked
How do you detect urea cycle defects?
The body usually removes ammonia as it is toxic but it is unable to remove such high levels of ammonia, it instead attaches an ammonium group to glutamate –> glutamine.
- Serum glutamine is high
- Serum amino acids in urea cycle will either be HIGH or ABSENT
- Urine orotic acid
How do you treat urea cycle disorders?
Remove ammonia (sodium benzoate, sodium phenylacetate or dialysis) Reduce ammonia production (low protein diet to stop urea formation)
What long term condition can be an indicator of urea cycle disorders?
Long-term psychiatric conditions
What are the key features/ symptoms of patient with urea acycle disorder?
Resp alkalosis Hyperammonaemia N+V Vomiting without diarrhoea Neurological encephalopathy Avoiding/change in diet
What is a metabolic acidosis + hyperammonaemia + high anion gap suggestive of?
organic aciduria
What are the three branch chained amino acids?
Leucine, Isoleucine and valine
What are organic acidurias often associated with?
Funny smelling urine e.g. cheesy or sweaty, due to the organic acids
What is an example of an organic aciduria?
Isovaleric acidaemia
Which enzyme is deficient/absent in isovaleric acidaemia?
Isovaleryl coA-dehydrogenase
How do organic acidurias generally present in neonates?
Unusual odour Lethargy Feeding difficulty Truncal Hypotonia/ limb hypertonia Myoclinic jerks pancytopaenia Neutropaenia Thrombocytopaenia Hypocalcaemia
What are the features of the chronic intermittent form of organic acidurias?
Recurrent episodes of ketoacidotic coma
Cerebral abnormalities
Reye syndrome
What is Reye syndrome?
Swelling of the liver and brain
What coudl trigger Reye syndrome?
Salicylates, antiemetics, valproate, symptom of metabolic disease
What is the Reye syndrome metabolic screen?
Plasma ammonia Plasmia/urine amino acids Urine organic acids Plasma glucose and lactate Blood spot carnitine profile
NOTE: The top 4 investigations should be performed during the acute state because the abnormal metabolites will disappear after a few days. Blood spot carnitine profile is the only measure which remains abnormal during remission!!
What do mitochondrial fatty acid Beta oxidation defects present with?
hypoketotic hypoglycaemia (unable to make ketones as unable to break down fatty acids)
Also presents with hepatomegaly and cardiomyopathy
What investigations would yu do for some one with mitochodnrial fatty acid beta oxidation defects?
Blood ketones
Urine organic acids
Blood spot acylcarnitine profile
Name two carbohydrate disorders
Galactosaemia and Glycogen storage disorder type 1 (von Gierke’s)
Most common galactosaemia
Galactose-1-phosphate uridyl transferaste (Gal-1-PUT) deficiency
What does Gal-1-PUT deficiency lead to high levels of?
Gal-1-phosphate levels
What do high Gal-1-phosphate levels lead to?
Liver and kidney disease, bilateral cataracts, also inhibits the immune response
What does Gal-1-PUT deficiency present with?
D&V
Hypoglycaemia
cBr + hepatomegaly
Sepsis
