Metabolic Disorders Flashcards
What is a metabolic disorder?
It is a disorder of any metabolic pathway in the body. It is usually the result of an enzyme being deficient which causes:
- Reduced concentration of the pathway end product
- Increased concentrations of the pre-cursors
- Increased enzyme activity as a result of increased pre-cursor concentration
What are the definitions of specificity, sensitivity, positive predictive value, negative predictive value? How do you calculate them?
Specificity:
- The probability that someone without the disease will correctly test negative
- True negative / (true negative + false positive)
Sensitivity:
- The probability that someone with the disease will correctly test positive
- True positive / (true positive + false negative)
Positive Predictive Value:
- The probability that someone who tests positive actually has the disease
- True positive / (true positive + false positive)
Negative Predictive Value:
- The probability that someone who tests negative actually does not have the disease
- True negative / (true negative + false negative)
What is currently screened for in the national new-born screening programme?
- Phenylketonuria
- Congenital hypothyroidism
- Cystic fibrosis
- Sickle cell disease
- Medium chain acylCoA dehydrogenase deficiency
What is classical phenylketonuria? What are the symptoms? How is it screened for?
It is a deficiency of phenylalanine hydroxylase, causing a build up of the toxic precursor phenylalanine. It can have no physical symptoms, but it heavily affects IQ (<50).
It is screened by testing the blood concentrations of phenylalanine.
What is cystic fibrosis? What are the symptoms? How is it screened for?
It is a mutation in the CFTR gene (6 types) causing more viscous secretions and blockages. It usually causes severe respiratory and pancreatic problems.
It is screened by testing the immune reactive trypsin (IRT) levels in the blood:
- If above 99.5th centile, DNA testing across 4 mutations
- If at least 2 mutations, CF diagnosis made
- If 1 mutation, DNA tests again against 28 mutations
- If 0 mutations, IRT tests again at days 21-28
What is mass spectrometry?
A laboratory test to give a unique footprint for a compound. It is used to diagnose MCADD
What is medium chain acetylCoA dehydrogenase deficiency? What are the symptoms? How is it screened for?
It is a deficiency in MCAD, causing an inability to break down fatty acids energy, causing a severely hypoglycaemic state, and sometimes cot death.
It is screened with mass spectrometry to test for blood levels of acylcarnitine.
How can you group different metabolic disorders?
- Accumulation of toxins
- Reduced energy stores
- Large molecule synthesis
- Defects in large molecule metabolism
- Mitochondrial
What are examples of metabolic disorders within the ‘accumulation of toxins’ category? What are their key features?
Organic acidaemias
- High urea, ketones
- Metabolic acidosis
- Funny smells
- Treat with low protein diet
Urea cycle disorders
- High ammonia
- Respiratory alkalosis
- Psychiatric disturbances
- Vomiting with no diarrhoea
- Treat with low protein diet and sodium benzoate
Aminoacidopathies
- High phenylalanine
- Retardation
- Funny smells
What are examples of metabolic disorders within the ‘reduced energy stores’ category? What are their key features?
Glycogen storage disorders
- Type 1: Von Gierke’s
- Hypoglycaemia with lactic acidosis
- Hepatomegaly
- Treat with CHO
Glacatossaemia
- Increased gal-1-phosphate
- Cataracts
- Hypoglycaemia
- Conjugated hyperbilirubinaemia
- Treat with low lactose diet
Fatty acid oxidation disorders
- Hypoglycaemia
- Low ketones
- Treat with regular CHO
What are examples of metabolic disorders within the ‘large molecule synthesis’ category? What are their key features?
Peroxisomal disorders
- Poor feeds
- Retinopathy
Glycosylation disorders
- Retardation
- Nipple inversion
What are examples of metabolic disorders within the ‘large molecule metabolism’ category? What are their key features?
Lysosomal disorders
- Very slow progressing
- Neuroregression
What are examples of metabolic disorders within the ‘mitochondrial’ category? What are their key features?
MELAS
POEMS
These involve the CNS, heart, muscle
Muscle biopsy to diagnose
What is Reye’s syndrome?
This is an example of an organic acidaemia, characterised by vomiting, lethargy, seizures and is triggered by salicylates, or other medications.
Test AT TIME OF ATTACK:
- Ammonia
- Amino acids
- Organic acids
- Blood glucose and lactate
Can test later:
- Carnitine
