Metabolic Disorders and Screening 1 and 2 Flashcards
What are the criteria for screening programmes called?
Wilson and Junger
What causes Phenylketonuria (PKU)?
Deficiency of phenylalanine hydroxylase
What does phenylalanine do?
Converts phenylalanine to tyrosine
What are key clinical features of PKU?
Low IQ Seizures Stunted growth Hyperactivity Musty odor of breath/skin/urine
How is PKU treated?
Monitor diet closely
Monitor phenylalanine intake
Treatment must be started within first 6 weeks of life
What is sensitivity?
True positives/total number of disease cases
What is specificity?
True negatives/total number without the disease
What is the positive predictive value?
True positives/total number with positive results
What is the Guthrie test and when is it done?
UK Newborn Screening
Heel prick test
Blood sample to screen for abnormalities
5-8 days of life
What illnesses are in the Newborn screening programme?
Congenital hypothyroidism Sickle cell disease Cystic fibrosis A series of metabolic disorders: MCAD deficiency Maple syrup urine disease Isovaleric acidaemia Glutaric aciduria type 1 Homocystinuria
What is MCAD deficiency?
Fatty acid oxidation disorder
What does MCADD classically result in?
Cot death due to hypoglycaemia
What gene is affected in cystic fibrosis?
Cystic fibroiss transmembrane conductance regulator (CFTR)
What test is used to screen for CF?
High immune reactive trypsinogen
What mutation most commonly causes CF?
Delta F508
What is the urea cycle responsible for?
Breaking down ammonia into urea
How many enzymes are in the urea cycle?
7
What is the genetic inheritance of urea cycle disorders?
Autosomal recessive except ornithin transcarbamylase (OTC) deficiency which is X-linked
How does the body react to hyperammonimia?
Attach glutamine to ammonia to make glutamine
What can be measured in the urine to look for urea cycle disorders?
Orotic acid
How are urea cycle disorders treated?
Remove the ammonia: sodium benzoate, sodium phenylacetate, or dialysis
Reduce ammonia production: low protein diet
With what groups of condition can hyperammonaemia be associated?
Long-term psychiatric illness
What are key features of urea cycle disorders?
Vomiting without diarrhoea Respiratory alkalosis Hyperammonaemia Neurological encephalopathy Avoidance of protein
What is an organic aciduria?
A defect within the complex metabolism of branched chain amino acids (leucine, isoleucine, and valine)
What are the amino acids excreted as in organic aciduria?
3-OH-isovaleric acid (cheesy/sweaty smell)
Isovaleryl glycine
How does a neonate present with organic aciduria?
Unusual odour Lethargy Feeding problems Truncal hypotonia Myoclonic jerks Hyperammonaemia with metabolic acidosis and high anion gap
What is Reye’s syndrome?
A rare disorder causing swelling of the brain and liver. Features include: - Vomiting - Lethargy - Confusion - Decerebration - Respiratory arrest
Can be triggered by drugs (salicylates) and viral illness.
What is included in a Reye Syndrome metabolic screen?
During acute episode: Plasma ammonia Plasma/urine amino acid Urine organic acids Plasma glucose and lactate
Any time:
Blood spot carnitine profile
What do mitochondrial fatty acid beta-oxidation defects cause?
Hypoketotic hypoglycaemia - unable to break down fatty acids
What do mitochondrial fatty acid beta-oxidation disorders do to the body?
Hepatomegaly
Cardiomyopathy
How many disorders of galactose metabolism are there?
3
What is the most common and severe form of galactose metabolism?
Galactose-1-phosphate uridyl transferase deficiency
What key feature to children galactose-1-phosphate uridyl transferase deficiency present with?
Conjugated hyperbilirubinaemia
What complication can occur in children if galactose-1-phosphate uridyl transferase deficiency is not picked up on?
Bilateral cataracts
How is mitochondrial DNA inherited?
Maternally
What does heteroplasmy mean?
You need a certain load of mitochondrial DNA to develop symptoms
