homozygous familial hypercholesterolaemia

Last reviewed 04/2021

This is very rare.

• the incidence of heterozygous familial hypercholesterolaemia (FH) in the UK is about 1 in 500
• the chances of two unrelated heterozygotes marryining is 1 in 250,000 (although the chances of two people meeting are higher when attending a specialist clinic!). The chance of conceiving a child is homzygous for FH is therefore 1 in 4 - thus the incidence of homozygous FH is estimated at about 1 in 1 million
• note that it is likely that the individuals with FH will have different LDL-receptor mutations and therefore the homozygous FH child would in fact be a compound heterozygote (i.e. would have inherited the different LDL-receptor mutation from each parent) although termed a FH homozygote. True FH homozygotes (i.e. each parent has the identical LDL-receptor mutation) are more likely to occur in situations where marriage within an extended family is the tradition (e.g. first-cousin marriage)

Individuals homozygous for familial hypercholesterolaemia develop coronary artery disease at a much earlier age than individuals heterozygous for this condition.

They often develop coronary artery disease as teenagers and have an extremely high cholesterol level (generally >16 mmol/l) and tendon xanthomas. They may also develop orange-yellow cutaneous planar xanthomata (especially in the antecubital and popliteal fossae, webs between fingers and buttocks) - also they may develop of the fronts of the kneens and palms of the hands during crawling.

Other possible features include:

• supravalvar aortic stenosis - may result in sudden death
• polyarthralgia
• may also be mildly raised levels of triglycerides and VLDL's.

In general, life expectancy is not usually extended beyond the early twenties. Myocardial infarction has occured as early as 2 years of age in an FH homozygote.

Management of FH homozygotes is very difficult and requires specialist supervision. As well as lipid lowering medication (e.g. statins) other techniques such as plasmapheresis or LDL apheresis and liver transplantation have been employed in management of patients with homozygous FH.