Also known as: Familial hypercholesterolaemia, familial combined hyperlipidaemia, sitosterolaemia« Back to test list
Hypercholesterolaemia is usually due a combination of multiple genetic and environmental factors i.e. “polygenic hypercholesterolaemia”, and genetic testing has little role to play in the management of such families.
There is a smaller and important group of hypercholesterolaemias that are due to mutations in any one of several genes i.e. these are single-gene disorders. This group includes autosomal dominant hypercholesterolaemia (“Familial Hypercholesterolemia”), lipaemic splenomegaly, familial defective apo B-100, sitosterolaemia, and some families with familial combined hyperlipidaemia.
The diagnosis of a specific familial dyslipidaemia is made on the basis of clinical history and biochemical findings. Genetic testing is not necessary to make this diagnosis.
This test result has implications regarding the aetiology and inheritance of dyslipidaemia in an individual, and the risk of dyslipidaemia and related disorders in a patient’s relatives.
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.
This test can assist in making a diagnosis in an affected patient. It may also provide useful risk information for unaffected relatives. Testing unaffected people to provide risk information may require that the clinician comply with guidelines provided by professional and regulatory authorities regarding pre-test counselling and consent. In particular, national regulations stipulate that carrier testing of an unaffected child requires the laboratory to have evidence of pre-test counselling by a genetics professional and written consent. For advice or assistance, please contact us on 1800 010 447.
In patients with familial hypercholesterolaemia, a pathogenic mutation can be identified in ~70% of cases.
Pathogenic mutations can be identified in >90% of patient with sitosterolemia.
Specific ApoE mutations are identified in ~30% of patients with lipaemic splenomegaly, and in ~2% of patients with familial combined hyperlipidaemia.
In an affected person with a clinical diagnosis, the presence of a pathogenic mutation confirms the diagnosis and may provide additional information regarding the risk of the disorder in relatives. However, the absence of a pathogenic mutation in such a patient does not necessarily exclude the clinical diagnosis.
In an unaffected person from a family with confirmed genetic diagnosis, the presence of the family’s mutation may indicate an increased risk of developing atherosclerosis, and close clinical follow-up may be warranted. The interpretation of such results depends on the particular gene and mutations. Pre-test genetic counselling is strongly recommended.
Please note that there is a separate panel of genes which cause familial hypertriglyceridaemia .
Analysis of a gene panel for sequence abnormalities and deletions/duplications.
This test is provided by Bioscientia, a Sonic Healthcare laboratory in Germany. Bioscientia is accredited within Germany and by the College of American Pathology for the provision of medical genetic tests.
This test is usually requested by a medical specialist with experience in the genetic management of dyslipidaemias, or a clinical geneticist.
2-5 mL blood in EDTA. Specimens may be collected by the requesting practitioner or at any Sonic Healthcare pathology collection centre.
To help ensure the quality of the test, a genetic test should be done with a dedicated sample whenever possible i.e. a sample collected specifically for that test rather than a sample that is used for multiple tests.
We also recommend that the patient or another adult check the labelling of request forms and sample tubes.
Please include a statement about family history (or absence of family history) of the disease in clinical details on referral form. If family history is present, please state relationship to patient.