ChemPath - Metabolic disorders Flashcards
When are metabolic disorders screened for and which ones are screened for
Guthrie spot at 6 days of age
- Sickle cell disease
- Congenital hypothryoidism - TSH levels
- Cystic fibrosis - immune reactive trypsin
- Medium chain acylCoA dehydrogenase deficiency (MCAD) - Acylcarnitine levels by tandem Mass Spectrometry
- Phenylketonuria (PKU) - phenylalanine levels
Define specificity
Probability (in %) that someone without the disease will correctly test negative
TN/(FP+TN)
Define sensitivity
Probability that someone with the disease will correctly test positive
TP/(TP+FN)
Define positive predictive values (PPV)
Probability that someone who tests positive actually has the disease
TP/(TP+FP)
Define negative predictive value (NPV)
Probability that someone who tests negative actually doesn’t have the disease
TN/(TN+FN)
What are the groups of metabolic conditions
- Accumulation of toxins
- Reduced energy stores
- Issues with large molecule synthesis
- Large molecule metabolism
- Mitochondrial
Which metabolic disorders are due to accumulation of toxins
Phenylketonuria (PKU)
Maple syrup urine (MSU)
Organic acidaemia
Urea cycle defect
What are the features of phenylketonuria and what is the management
Deficiency in phenylalanine hydroxylase → phenylalanine accumulation
Blue eyes and fair hair/skin
Retardation
Mx: restrict phenylalanine
What are the features of maple syrup urine
Sweaty feet
What are the features of organic acidaemia and what is the management
Branch chain amino acid metabolism defect → reduced amino acid breakdown → high urea and ketones → metabolic acidosis
Funny smelling urine
Raised anion gap
Mx: low protein diet, acylcarnitine and haemofiltration
What are the features of urea cycle disorders and what is the management
Autosomal recessive
Ammonia accumulation → encephalopathy and developmental delay
Respiratory alkalosis
Vomiting, diarrhoea
Mx: low protein diet
What metabolic disorders are due to reduced energy stores
Medium chain acylCoA dehydrogenase deficiency (MCADD)
Galactosaemia
Glycogen storage disease
What are the features of MCADD and what is the management
Unable to oxidise fatty acids → reduced ketone production → low ketones and raised acyl carnitine
Cardiomyopathy, rhabdomyolysis
Mx: increase regular carbohydrate intake, avoid hypoglycaemia
What are the features of Galactosaemia and what is the management
Unable to metabolise galactose → raised galactose phosphate
Liver and kidney disorder
Hypoglycaemia
Untreated → bilateral cataract
Galactose in urine
Mx: low lactose/galactose diet i.e. low milk
What are the features of glycogen storage disease (including Von Gierke’s) and what is the management
Glucose-6-phosphatase deficiency → unable to liberate glycogen from liver or muscle → accumulation of glycogen in the liver
Hepatomegaly → High risk of hepatoblastoma
Hypoglycaemia
Lactic acidosis
Mx: high carbohydrate diet
