familial dysbetalipoproteinaemia

Last edited 09/2021 and last reviewed 10/2023

This condition is characterised by raised triglyceride and cholesterol levels due to abnormally high concentration of IDL and chylomicrons. It is inherited as an autosomal recessive trait.

This is a type III hyperlipidaemia according to the WHO classification

• more than 90% of dysbetalipoproteinaemic patients are homozygous for apoE2
  • however only a minority of apoE2 homozygotes will be overtly hyperlipidaemic

This disease may present in early adult life with possible other features such as

• obesity, glucose intolerance and hyperuricaemia
• yellow palmar creases, palmer xanthomas and tuberoeruptive xanthomas may be present
• there is an increased risk of coronary artery disease (this condition may be found in approximately 3% of survivors of myocardial infarctions) and peripheral vascular disease.

Diagnosis:

Type III hyperlipoproteinaemia (remnant removal disease) should be suspected in an individual with (1):

• mixed hyperlipidaemia (serum total cholesterol >8 mmol/l and serum triglyceride >5 mmol/l) - though generally lipid levels are markedly raised e.g. cholesterol 10-20mmol/L and triglycerides 15-40 mmol/L
  • note that though the genotype that can lead to these markedly raised lipids is present in about 1% of the population that there is often a metabolic insult required before the dyslipidaemia associated with the genotype to be become manifested - the most common causes of a precipitation of marked raised lipids (and manifestation of a type III hyperlipidaemia) are uncontrolled diabetes, undiagnosed hypothyroidism or alcohol excess
    
    
• possible features include - palmar striae and/or tuberoeruptive xanthomata, remnant (floating Beta) lipoprotein, or defective apo E isoforms

Management:

• seek specialist advice
• statins are not generally very effective in the management of a type III hyperlipidaemia because of the mechanism of the hyperlipidaemia being related to excess VLDL particles (see linked item)
• there is generally a precipitant for the marked dyslipidaemia (see above) and this should be sought
• first-line treatment is usually with addition of a fibrate or fish oil
• a pragmatic management of the dyslipidaemia would be (2):
  • seek specialist advice
    • level of triglycerides at which to refer for specialist advice (fasting level of >= 10 mmol/l (routine review); >= 20 mmol/l (urgent review)
    • criteria for urgent review
      • NICE suggest that refer for urgent specialist review if a person has a triglyceride concentration of more than 20 mmol/litre that is not a result of excess alcohol or poor glycaemic control (3)
    • criteria for non-urgent review
      • a guideline relating to management of raised triglycerides in type 2 diabetes (4) states:
        • because of the significant risk of pancreatitis, those with type 2 diabetes and triglyceride (TG) levels >=10 mmol/l should be considered for referral to a specialist lipid clinic
  • identify if a metabolic insult that has led to significant dyslipidaemia and manage accordingly
  • if currently on a statin then:
    • add a fibrate e.g. fenofibrate 267 mg per day
      • fibrates should be used with caution in renal impairment (can cause a deterioration in eGFR) - in this circumstance then fish oils would be the preferred intervention
    • continue statin - consider doubling dose of statin
    • combination therapy with a fibrate and statin is associated with increased myopathy risk - counsel the patient about this with red flag advice for seeking urgent review and stopping lipid lowering medication if symptoms suggesting of myositis/rhabdomyolysis
      • often patient is told to take the fibrate in the morning and the statin in the evening in order to theoretically reduce the risk of interaction although this based on expert concensus rather than trial evidence
    • check lipids and review within two weeks

Reference:

1. Durrington, PN (1995). Hyperlipidaemia: diagnosis and management. 2nd edition. Butterworth-Heinemann Limited.
2. Dr Jim McMorran - Editor of GPnotebook and GPSI Diabetes and Lipids (Coventry and Warwickshire NHS Partnership Trust) (July 26th 2019).
3. NICE (May 2014).Lipid modification - Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
4. Sinclair A et al. Management of elevated serum triglycerides in type 2 diabetes: A pragmatic approach Diabetes & Primary Care, 2012, Vol 14, No 4, pages 223-234.