What is the history of Familial Hypercholesterolemia?

Familial Hypercholesterolemia (FH) was first clinically characterized in the late 19th century, with its genetic basis identified in the 1970s by Nobel laureates Michael Brown and Joseph Goldstein. Their groundbreaking research into how the body clears cholesterol transformed Familial Hypercholesterolemia from a mysterious condition into a manageable genetic disorder.

When was Familial Hypercholesterolemia first identified?

The clinical features of Familial Hypercholesterolemia were first described in the 1870s, notably by Sir William Gull and later by Charles Fagge, who observed the characteristic skin deposits known as xanthomas. For decades, physicians struggled to understand why some families suffered from premature heart disease despite appearing otherwise healthy. It wasn't until the 1930s that Carl Müller established the autosomal dominant inheritance pattern, confirming that Familial Hypercholesterolemia was a genetic condition rather than just a result of poor diet.

How did our understanding of Familial Hypercholesterolemia evolve?

The true turning point in our understanding occurred in 1973. Michael Brown and Joseph Goldstein discovered the LDL receptor, explaining exactly how the body removes cholesterol from the blood. Their work revealed that patients with Familial Hypercholesterolemia have defective or missing receptors, causing cholesterol levels to skyrocket from birth. This discovery earned them the Nobel Prize in Physiology or Medicine in 1985 and remains the foundation for modern lipidology.

What are the major milestones in treating Familial Hypercholesterolemia?

Treatment for Familial Hypercholesterolemia has advanced significantly over the last century:

• 1970s: The development of apheresis, a dialysis-like procedure to physically remove cholesterol from the blood.


• 1987: The FDA approval of statins, which revolutionized the management of high cholesterol.


• 2015: The introduction of PCSK9 inhibitors, a class of injectable medications that significantly lower LDL levels in patients who cannot tolerate or do not respond to statins.

How has patient advocacy changed the landscape?

Historically, patients were often told their condition was a "lifestyle choice," leading to significant stigma. Today, organizations like the FH Foundation and the community here at DiseaseMaps.org—where 14 individuals have shared their experiences—have shifted the focus toward early screening. We now know that identifying Familial Hypercholesterolemia in childhood can prevent life-threatening cardiovascular events in adulthood.

Next steps

• Consult a lipidologist or cardiologist to discuss your family history and lipid profile.


• Request a cascade screening test if you have a family member diagnosed with Familial Hypercholesterolemia.


• Join the DiseaseMaps.org community to connect with others navigating life with this condition.

Medical disclaimer: This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Familial Hypercholesterolemia


• OMIM (Online Mendelian Inheritance in Man): Familial Hypercholesterolemia (#143890)


• The FH Foundation: Understanding the History and Genetics of FH


• Orphanet: Familial Hypercholesterolemia