What blood tests are done for familial hypercholesterolaemia (FH)? 

In the UK, familial hypercholesterolaemia (FH) is diagnosed using two main types of blood tests: a lipid profile and genetic DNA testing. Initially, a lipid profile is conducted to identify significantly elevated LDL cholesterol levels. If these levels meet specific clinical criteria such as the Simon Broome or Dutch Lipid Clinic Network scores a genetic blood test is then performed to confirm the presence of a known gene mutation that causes the condition. 

What We’ll Discuss in This Article 

• The role of the initial lipid profile in identifying FH. 

• Specific LDL cholesterol thresholds for adults and children. 

• How genetic testing confirms the diagnosis and identifies the causative gene. 

• The five key genes screened in the UK’s National Genomic Test Directory. 

• The process of cascade testing for first-degree relatives. 

• Differentiating between monogenic FH and polygenic high cholesterol. 

• Secondary blood tests used to exclude other causes of high lipids. 

The Initial Lipid Profile Screening 

The diagnostic journey for FH almost always begins with a standard lipid profile. This test measures the concentrations of total cholesterol, HDL (good) cholesterol, and LDL (bad) cholesterol. Because FH is a genetic condition present from birth, the LDL levels are typically much higher than those found in standard age-related high cholesterol. 

Under the Simon Broome criteria, which are widely used by the NHS, a clinical diagnosis of ‘possible’ FH is considered if your blood results show: 

• Adults: Total cholesterol above 7.5 mmol/L or LDL cholesterol above 4.9 mmol/L. 

• Children (under 16): Total cholesterol above 6.7 mmol/L or LDL cholesterol above 4.0 mmol/L. 

According to HEART UK (2025), ‘A lipid profile is the first step in finding the one in 250 people in the UK living with FH, many of whom are unaware of their risk.’ 

Genetic Confirmation and DNA Testing 

If the initial lipid results and family history suggest a high likelihood of FH, the NHS provides specialist genetic testing. This is a highly specific blood test that looks for alterations in the genes responsible for clearing LDL cholesterol from the blood. 

In the UK, the National Genomic Test Directory (2026) specifies that genetic testing for FH (Test Code R134) focuses on five primary genes: 

Gene	Function in the Body	Prevalence in FH
LDLR	Provides instructions for making LDL receptors that clear cholesterol.	Most common cause (>90%)
APOB	Helps the LDL particle bind to its receptor in the liver.	Approx. 5-10% of cases
PCSK9	Regulates the number of LDL receptors on the surface of liver cells.	Less common (<5%)
APOE	Involved in the transport and metabolism of lipids.	Rare cause
LDLRAP1	Assists the LDL receptor in moving cholesterol into the cell.	Rare (Autosomal recessive)

A positive genetic test provides a ‘definite’ diagnosis of FH. This is crucial because it allows the NHS to offer cascade testing to your relatives, who have a 50% chance of carrying the same gene. 

Causes and Triggers of FH 

Unlike standard high cholesterol, which is often triggered by diet or lack of exercise, FH is caused by a single inherited mutation. This means the ‘trigger’ is present at conception. However, while the cause is genetic, lifestyle factors can still worsen the condition. 

• Primary Cause: An inherited mutation that results in fewer or malfunctioning LDL receptors in the liver. 

• Secondary Triggers: While they do not cause FH, factors like a high-saturated-fat diet, smoking, and physical inactivity can significantly increase the already high cardiovascular risk associated with the condition. 

• Hormonal Changes: Significant life events like pregnancy or the menopause can trigger further fluctuations in lipid levels for those with an underlying FH mutation. 

FH vs. Polygenic High Cholesterol 

It is important to differentiate between monogenic FH (caused by one major gene) and polygenic high cholesterol (caused by many small genetic variations). 

Feature	Monogenic FH	Polygenic High Cholesterol
Genetic Cause	One clear mutation (e.g., LDLR).	Multiple small genetic variants.
Lipid Levels	Very high from birth.	Gradually rises with age and lifestyle.
Family History	Strong pattern of early heart disease.	Variable family history.
Genetic Test Result	Likely positive for a specific gene.	Negative for major FH genes.

To Summarise 

Diagnosing FH in the UK involves a two-step blood testing process: an initial lipid profile to check for very high LDL levels, followed by a specialist genetic test to identify a specific mutation in genes like LDLR or APOB. These tests are essential for confirming a diagnosis and enabling cascade screening for family members. Early identification through these blood tests allows for life-saving treatment to begin as early as possible. 

If you experience sudden, crushing chest pain or signs of a stroke like facial drooping or arm weakness, call 999 immediately. 

You may find our free BMI Calculator helpful for monitoring your general health, although FH management primarily focuses on clinical lipid targets rather than weight alone. 

Authority Snapshot 

Dr. Rebecca Fernandez is a UK-trained physician with an MBBS and experience in general surgery, cardiology, internal medicine, gynecology, intensive care, and emergency medicine. She has managed critically ill patients, stabilised acute trauma cases, and provided comprehensive care across inpatient and outpatient settings. This guide is based on 2026 clinical standards from the NHS and NICE to ensure the public receives accurate information regarding genetic and lipid testing for inherited conditions.