Care for rare: personalised medicine for inherited metabolic diseases

Question 1

What is FAO Disorders?
- give an example of one

Answer 1

Fatty acid oxidation disorders
- VLCAD
- enzymes of mitochondrial fatty acid ß- oxidation
- defective breakdown of long-chain fatty acids
- rare 1/ 50 000
- autosomal recessive

◦ cannot break long CoA into short
◦ energy shortage because lack of break-down
◦ accumulation acyl CoA in mitrochondia - toxicity
◦ after accumulation system can turn around

Question 2

What the the most common clinical and biomedical consequences of FAO disorders?

Answer 2

• mild/ severe phenotypes
• symptoms often triggered by catabolism (fasting, sports, infection)

Pathophysiological Mechanisms:
- energy shortage
- accumulation of acylcarnitines

Clinical Deficiency:
- Liver: hypoglycaemia –> problem baby without reserves
- Heart: cardiomyopathy & arrhythmia
- Muscle: myopathy & myoglobulinuria, myalgia, exercise intolerance, muscle weakness, fatigue

Question 3

Explain the factors that contribute to clinical variability in FAO disorders

Answer 3

• level of severity
• work different under different heat conditions
  – incomplete –

Question 4

what are the main therapeutic strategies for FAO disorders and what are they modes of action?

Answer 4

ketones as alternative energy sources
- fuels TCA cycle
- spairing of glycogen

– incomplete –

Question 5

What are the pro’s and con’s of FAO’s being included in the hielprik test?

Answer 5

+ Prevent early-life complications
+ We know all Dutch patients and can use their cells

• Cannot prevent late-life complications
• How to predict future disease?