Very high cholesterol, tendon xanthomata and a family history of early death
Expansion
Suspect it when
- Total cholesterol above 7.5 mmol/l in an adult, or LDL above 4.9
- A family history of premature coronary disease: under 60 in a first degree relative or under 50 in a second degree relative
- Tendon xanthomata in the patient or a first or second degree relative
- Sudden cardiac death in a young relative
Simon Broome criteria combine the cholesterol level with tendon xanthomata (definite), or with the family history (possible), or with DNA confirmation.
“Tendon xanthomata are specific; xanthelasma is not.” Tendon xanthomata over the Achilles tendon and the extensor tendons of the hand are close to pathognomonic, whereas xanthelasma and corneal arcus occur commonly without any lipid disorder, particularly with age.
It is autosomal dominant, most often an LDL receptor mutation, with a prevalence of about 1 in 250 heterozygotes, so it is far commoner than usually assumed.
Cascade testing of first degree relatives is mandatory, and this is one of the few situations where the diagnosis in one patient obliges systematic testing of a family.
Treatment is high intensity statin from diagnosis, with ezetimibe and PCSK9 inhibitors where targets are not met, aiming for a 50 per cent reduction in LDL. Homozygotes present in childhood and need specialist care.