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Familial hypercholesterolaemia

Also known as: FH, hyperlipidaemia, LDLR, APOB, PCSK9, LDLRAP1

Test category:

Familial - Hyperlipidaemia, Cardiac

Use of test

Purpose:

Hypercholesterolaemia is usually due a combination of multiple genetic and environmental factors i.e. polygenic hypercholesterolaemia.

However, there is an important group of patients with hypercholesterolaemia due to mutations in any one of several genes: LDLR, APOB, PCSK9 and LDLRAP1. Hypercholesterolaemia that can be attributed to a single gene is called “familial hypercholesterolaemia”, or “FH”. The identification of such mutations has major clinical implications for the management of the index patient and their relatives.

Mutations in the LDLR, APOB and PCSK9 genes are inherited in an autosomal dominant fashion. The first-degree relatives of a patient with a mutation in one of these genes are at 50% risk of inheriting the mutation and developing FH. Second-degree relatives are also at increased risk. Mutations in LDLRAP1 are inherited in an autosomal recessive fashion, with siblings of the index patient being at 25% risk of developing FH.

For an overview for doctors of the genetic management of familial hypercholesterolaemia, please click here. For an overview for patients, please click here.

Utility:

Diagnostic testing i.e. testing of individuals with clinically confirmed or suspected FH, can provide important information to guide the current therapy of the patient and the risk of FH among relatives. Patients with genetically confirmed FH have a higher cardiovascular disease risk than non-FH patients for a given LDL-cholesterol level. They warrant aggressive therapy and monitoring. The documentation of a pathogenic mutation may also help the patient meet PBS requirements for access to certain medications. The Dutch Lipid Clinic Network score  is a widely used algorithm for combining clinical and laboratory data to estimate the probability that a patient has FH.

Predictive/Cascade testing i.e. testing of relatives for mutations already identified in the family, provides valuable information regarding the risk of FH. The early identification and treatment of people with such mutations reduces the long-term risk of cardiovascular disease. 

Ethical considerations:

This is an assay for heritable mutations. It may raise issues of ethics or consent that are different from most other investigations ordered in the routine care of a patient.

Pre-test counselling by either an experienced clinician or an accredited genetic counsellor is required, together with signed informed consent for testing. If providing the pre-test counselling yourself, please use the Sonic Genetics consent form and enclose the completed form with the request or email to geneticcounselling@sonicgenetics.com.au. Pre- and post-test genetic counselling are available through Sonic Genetics at no additional charge. There is no need to provide a completed consent form if pre-test counselling is being provided through Sonic Genetics.

For advice or assistance regarding counselling or informed consent, please contact us on 1800 010 447.

Consent form:

Download the Sonic Genetics consent form.

Methodology:

Sequencing of the coding and exon/intron boundaries of LDLR, APOB, PCSK9 and LDLRAP1, and deletion/duplication analysis of LDLR. The test is performed in our NATA accredited Australian laboratory.

Requesting the test

Diagnostic testing is usually requested by a medical specialist with experience in the management of hypercholesterolaemia. Requests for rebated testing must be made by a medical specialist.

Predictive/Cascade testing can be requested by any doctor.

Please use the specific familial hypercholesterolaemia test request form (preferred).

OR:

Use a standard pathology request form and provide information as noted in the special instructions below.

Sample required:

2 x 4 mL blood in EDTA (independently collected in the case of predictive testing). Specimens may be collected by the requesting practitioner or at any of the national Sonic Healthcare pathology collection centres.

To help ensure the quality of the test, a genetic test should be done with a dedicated sample i.e. a sample collected specifically for that test rather than a sample that is used for multiple tests.

We recommend that the patient or another adult check the labelling of request forms and sample tubes. 

>Link to Sonic Healthcare collection centres

Special instructions:

When completing the request form, please indicate

  • whether testing is for diagnostic or predictive purposes
  • whether the request meets Medicare requirements for rebated testing
  • relevant clinical and laboratory data as this will help inform the interpretation of the gene test
  • For diagnostic testing, please include the Dutch Lipid Clinic Network score.

Please ensure that the patient has signed the request form and, if pre-test genetic counselling has been provided by the requesting doctor, a copy of the completed Sonic Genetics consent form is sent to the laboratory. The laboratory can provide pre- and post-test genetic counselling by phone on request at no additional cost to the patient. If signed informed consent is not received with the test request, the laboratory will contact you to confirm that genetic counselling will be provided through the laboratory.

Requests for predictive testing must be accompanied by documentation of the family’s mutation e.g. a reference number from Sonic Genetics or a copy of the relative’s test report.

 

Turnaround time:

4 - 6 weeks from receipt of sample into the laboratory and confirmation of informed consent.

 
Price:

This test has a Medicare rebate which, subject to the requirements of a Medicare descriptor being met, may cover all of the cost, inclusive of genetic counselling if required. Please note that requests for rebated diagnostic testing can only be received from a specialist. Requests for rebated predictive testing can be received from any doctor.

For non-rebated testing, the price is $1,200 inclusive of genetic counselling if required, which must be pre-paid. Should the patient elect not to proceed with the test after genetic counselling, the patient can apply for a partial refund; an administrative fee will be retained to cover the costs of genetic counselling.

Rebate:

For details of the Medicare rebate available, please click here:

Click here for our billing policy.