The diagnosis and treatment of familial dysbetalipoproteinaemia is challenging but very important
Autosomal dominant Familial Dysbetalipoproteinemia: a pathophysiological framework and practical approach to diagnosis and therapy
Koopal C, Marais DA, Westerink J, et al.
J Clin Lipidol. 2016; published online ahead of print
Phenotype and genotype of familial dysbetalipoproteinaemia (FD) [1-3]FD is a genetic lipid disorder associated with a 10-fold increased risk for premature atherogenic diseases compared to population-based controls and is characterised by:
- a lipoprotein phenotype of mixed hyperlipidaemia
- a genotype that consists of mutations in the apolipoprotein E gene (APOE).
Diagnostic challenges in autosomal dominant FD [4,5]Diagnosing autosomal dominant FD (ADFD) is important because:
- ADFD patients have the same atherogenic lipid profile as recessive FD patients. As a consequence they are exposed to the same increased risk of atherosclerosis.
- There are specific lipid treatment targets and lipid-lowering treatments for FD.
- Diagnosing ADFD will have consequences for family members due to the dominant inheritance of the disease.
- The wide variety in clinical presentations ranging from palmar crease, eruptive, cutaneous, or tendon xanthomata, to pancreatitis and premature atherosclerosis.
- FD is part of any differential diagnosis of mixed dyslipidaemia. The alternative explanations for an altered lipid phenotype can mask the presence of FD.
- Dominant inheritance pattern in a disease that is usually recessive.
- There are many ways to diagnose the lipid phenotype in FD, which vary in reliability and practicality.
- Routine genotyping methods may not detect ADFD.
- ADFD may be mistaken for familial hypercholesterolemia.
Treatment of autosomal dominant FD Treatment goals:
- Primary treatment goal: non-HDL-C <3.3 mmol/L
- Alternative treatment goal: TG <2.0 mmol/L
- Low-glycaemic diet and modification of secondary factors (obesity, insulin resistance, hypothyroidism)
- Pharmacological therapeutic options: the treatment of choice for FD is a combination therapy of statins and fibrates
- The final component of ADFD treatment is family counselling, because first degree relatives of ADFD patients have a 50% risk of developing ADFD. When diagnostic characteristics of ADFD are present in family members, an APOE gene sequence should be performed and, when ADFD is confirmed, adequate treatment should be initiated.
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