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Homozygous Familial Hypercholesterolemia

Information for
Healthcare Professionals

Is HoFH hiding in your practice?

Caregiver Story

HoFH: A Caregiver
Story

Watch this video featuring Karen, a
caregiver to two sons with HoFH, sharing
her journey from early symptoms to
diagnosis and ongoing care.

Homozygous familial hypercholesterolemia (HoFH) is an ultra rare, inherited genetic disorder of lipid metabolism1,2

HoFH is characterized by:1-4

  • Markedly elevated plasma levels of LDL-C (untreated LDL-C >10 mmol/L)3
  • Premature atherosclerotic cardiovascular disease and cardiovascular morbidity and mortality
  • Cholesterol buildup:
    • around the joints and on the tendons (xanthomas)
    • in the eyes (corneal arcus) and around the eyelids (xanthelasmas)

The current estimated prevalence of HoFH is 1 in 300,000.4

Prevalence is higher in these groups:

  • 1 in 275,000 French Canadians5
  • 1 in 30,000 Afrikaners in South Africa6
  • 1 in 100,000 Christian Lebanese7
Learn how to identify and diagnose HoFH

HoFH is an inherited lipid disorder

HoFH occurs when two pathogenic variants bearing the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent.1

Review the genetics and pathogenesis of HoFH

HoFH differs from HeFH

Homozygous FH (HoFH)3 Heterozygous FH (HeFH)3
Pathogenic variants inherited from both parents Pathogenic variant inherited from one parent
Occurs in 1 in 300,000 persons Occurs in 1 in 250 persons
LDL-C >10 mmol/L (untreated) LDL-C cholesterol ≥4.1 mmol/L in children
LDL-C cholesterol ≥4.9 mmol/L in adults
Likely physical symptoms, such as cholesterol deposits in the eye, tendons, knees, elbows and/ or between fingers and toes; these deposits are not always present May have physical symptoms, such as cholesterol deposits in the eye, tendons, knees, elbows and/or between fingers and toes
Treatment at time of diagnosis, no matter the age, with a specialist Treatment as early as age 10

Adapted from McGowan and Cuchel et al.

See the impact of HoFH

Look for HoFH in your practice

Physical signs and risk factors associated with HoFH:1,3,8

  • Untreated LDL-C >10 mmol/L – lower levels should not be discounted if other factors are present
  • Cutaneous or tuberous xanthomas – highly suggestive of HoFH in children
  • Corneal arcus – highly suggestive of HoFH
  • Evidence of CVD – in young children early signs and symptoms are linked to aortic stenosis and regurgitation
  • Family history of premature CVD
  • Family history of HeFH
Learn more about the management of HoFH

References

1. Cuchel M et al. Eur Heart J. 2023;00:1–15; 2. Raal FJ et al. Atherosclerosis. 2018;277:483–492; 3. McGowan MP et al. J Am Heart Assoc. 2019;8:e013225; 4.Tromp TR et al. The Lancet. 2022;399:719-728; 5. Moorjani S et al. Arteriosclerosis. 1989;9:211-6; 6. Seftel HC et al. Br Med J. 1980;281:633-6; 7. Slack J. Atheroscler Rev, 1979;5:35–66; 8. France M et al. Atherosclerosis. 2016;255:128–139;