Chemical Pathology - Metabolic Disorders Flashcards
When is the Guthrie blood spot test taken?
At 6 days of age
What conditions are screen for in the Guthrie blood spot test?
- Phenylketonuria
- Congenital hypothyroidism
- Cystic fibrosis
- Sickle Cell disease
- MCAD (medium chain acylCoA dehydrogenase) deficiency
What is the outcome of phenylketonuria and what is the screening test?
Outcome:
- Phenylalanines hydroxylase deficiency
Screening Test:
- Phenylalanine levels
What is the outcome of congenital hypothyroidism and what is the screening test?
Outcome:
- Dysgenesis/agenesis of thyroid gland
Screening Test:
- TSH levels
What is the outcome of cystic fibrosis and what is the screening test?
Outcome:
- Mutation in CTFR results in viscous secretions + causes ductal blockages
Screening Test:
- Immune reactive trypsin
- If +ve leads to DNA mutation detection
What is the outcome of medium chain AcylCoA dehydrogenase deficiency (MCADD) and what is the screening test?
Outcome:
- Fatty acid oxidation disorder
Screening Test:
- Acylcarnitine levels by tandem
- Mass Spectrometry
What is specificity?
- The probabilty that someone without the disease will correctly test negative
- TN/(FP+TN)
What is sensitivity?
- The probability that someone with the disease will correctly test positive
- TP/(TP+FN)
What is the positive predictive value (PPV)?
- The probability that someone who tests positive actually has the disease
- TP/(TP+FP)
What is the negative predictive value (NPV)?
- The probabililty that someone who tests negative actually doesn’t have the disease
- TN/(TN+FN)
What are the five different groups of metabolic diseases?
- Group 1: Accumulation of toxins
- Group 2: Reduced energy stores
- Group 3: Large molecule synthesis (all dysmorphic)
- Group 4: Defects in large molecule metabolism
- Group 5: Mitochondrial
What are the three different types of Group 1 metabolic disorders (accumulation of toxins) + their features?
Organic Adicaemias:
- High urear + ketones
- Metabolic acidosis
- Tx: low protein diet + acylcarnitine + haemofiltration
- Funny smells (due to organic acids)
Urea Cycle disorders:
- High ammonia leading to encephalopathy + developmental delay
- Respiratory alkalosis
- ?Vomiting + diarrhoea
- Tx: Low protein diet (stops urea formation)
Aminoacidopathies:
- High phenylalanine
- Blue eyes + fair hair/skin
- Retardation
- MSUD causes sweaty feet
What are the three different types of Group 2 Metabolic Disorders (reduced energy stores) + their features?
Glycogen storage disorders:
- Hypoglycaemia + lactic acidosis
- Hepatomegaly
- Developmental delay
- High risk: Hepatoblastoma
- Tx: Regular CHO
Galastossaemia:
- Increased Gal-1-phosphate levels
- Causes cataracts, hypoglycaemia, neonatal conjugated jaundice
- Test urine reducing agents
- Tx: Low lactose/galactose diet
Fatty acid oxidation disorders:
- Hypoglycaemia, cardiomyopathy, rhabdomyolysis
- Low ketones
- Screened with blood acylcarnitine
- Test urine organic acids
- Tx: Regular carbohydrate
What are two different types of Group 3 metabolic disorders (large molecule synthesis) + their features?
Peroxismal disorders (can’t catabolise very long fatty acids/make bile acids):
- Poor feeds
- Retinopathy
- Hepatomegaly
- Mixed hyperbilirubinaemia
Glycosylation Disorders:
- Measure serum transferrin
- Leads to retardation + nipple inversion
What are group 4 metabolic disorders (defects in large molecule metabolism) + their features?
Lysosomal disorders
- V. slow progressing
- Neuroregression
- Hepatosplenomegaly
- Cardiomyopathy
- Test urine mucooligopolysaccharides + WBC
- Enzyme levels
