Metabolic Disorders and Screening 2 Flashcards
What is the overall function of the urea cycle?
Take ammonia
Produce urea
What occurs when the urea cycle malfunctions (due to enzyme deficiency)?
HIGH AMMONIA
ammonia is very toxic
What is the mode of inheritance for urea cycle disorders?
Most are autosomal recessive
ONE X linked disorder: OTC deficiency
What is produced by the body when ammonia quantity is high?
GLUTAMINE
because ammonia binds to glutamate to make glutamine
this is part of the body’s attempt to excrete ammonia
What can you measure to detect urea cycle defect?
Glutamine
Urine orotic acid
How do you treat urea cycle defect?
FIRST LINE: remove ammonia using sodium benzoate / sodium phenylacetate
AFTERWARDS: reduce ammonia production via low protein diet
What are key clinical features of urea cycle disorders?
Vomiting without diarrhoea Resp alkalosis Hyperammonaemia Neurological encephalopathy Avoidance/Change in diet (e,g. avoiding protein, taking protein supplements)
What defects cause hyperammonaemia with metabolic acidosis and high anion gap?
defects In leucine, isoleucine, valine structures
ORGANIC ACIDURIAS
What do organic acidurias present as in neonates?
Unusual odour of urine lethargy feeding problems truncal hypotonia / limb hypertonia myoclonic jerks Cytopoenia
What does Reye syndrome present as’
vomiting lethargy increased confusion seizures decerebration respiratory arrest
Encepalopathy + liver failure
What is Reye Syndrojme triggered by?
aspirin
anti-emetics
valproate
Who does Reye Syndrome occur in?
Children <14
Esp after chicken pox/flu
Triggered. by aspirin
What metabolic presentation occurs with MCAD deficiency?
Hypoketotic hypoglycaemia
What occurs in hypoglycaemic patients with MCAD?
They are unable to break down fatty acids , so they cannot make ketones even if they are hypoglycaemic
What is the most common deficiency for galactosaemia?
Gal-1-PUT deficiency
Cannot break down carbohydrates
How does galactosaemia present?
Liver disease: vomiting , hepatomegaly, conj hyperbilirubinaemia
hypoglycaemia
sepsis
diahrroez
What becomes raised in Gal-1-PUT deficiency
Gal-1-P
What does Gal-1-P excess cause?
Liver, kidney disease bilateral cataracts (due to aldolase buildup)
how do you treat galactosaemia?
Avoid galactose (milk)
What is von Gierke’s disease?
Glycogen storage disease Type 1
inability to break down glycogen
What glycemic state are people with Von Gierke’s?
HYPOgycaemic
+ lactic acidosis
because they can’t tap into their glycogen reserves in liver and skeletal muscle
What is a mitochondrial disorder that occurs at birth?
Barth - cardiomyopathy, neutropenia, myopathyu
What is a mitochondrial disorder that occurs t 5-15 yo?
MELAS
What does MELAS present as?
Mitochondrial Encephalopahty
Lactic Acid
Strokes
What is a mitochondrial disorder occurring at 12-30 yo?
Kearns- Sayre
Chronic progressive opthalmoplegia
retinopathy
deafness
ataxia
What is lactate like in metabolic disorders?
HIGH
What o cc urs to ATP and thereby to tissues in metabolic disorder?
Defective ATP production
Causes multisystem disease esp affecting organs with high energy requirement
