Familial hypercholesterolaemia with high triglycerides: A diagnostic challenge

Area of Science:

• Cardiology
• Genetics
• Metabolic Disorders

Background:

• Combined or mixed hyperlipidaemia involves high cholesterol and triglyceride levels, affecting about 1% of the UK population.
• Often secondary to metabolic syndrome, diabetes, or alcohol use, it can also indicate primary conditions like familial combined hyperlipidaemia (FCH) or type III hyperlipidaemia.
• A critical differential diagnosis is familial hypercholesterolaemia (FH) with co-existing hypertriglyceridaemia from other causes.

Purpose of the Study:

• To report cases of genetically confirmed familial hypercholesterolaemia (FH) presenting initially with hypertriglyceridaemia.
• To discuss diagnostic challenges in identifying FH when hypertriglyceridaemia is present.
• To emphasize the importance of directly measuring LDL-C for accurate FH diagnosis in such scenarios.

Main Methods:

• Case series reporting four patients with genetically confirmed familial hypercholesterolaemia (FH).
• Patients initially presented with mixed hyperlipidaemia, including elevated triglycerides.
• Diagnostic approach involved genetic testing and direct measurement of low-density lipoprotein cholesterol (LDL-C).

Main Results:

• Four cases of familial hypercholesterolaemia (FH) were identified in patients with initial presentation of hypertriglyceridaemia.
• These patients exhibited high total cholesterol and LDL-C concentrations alongside moderately elevated triglycerides.
• Genetic testing confirmed the FH diagnosis in all reported cases.

Conclusions:

• Familial hypercholesterolaemia (FH) can be masked by concurrent hypertriglyceridaemia, posing diagnostic challenges.
• Directly measuring LDL-C is essential for accurate diagnosis in patients with mixed hyperlipidaemia.
• Early and accurate diagnosis of FH is critical for timely intervention and management.