Why INFOHaem™ MSS FH1536™

Why INFOHaem™ MSS FH1536™?

Familial Hypercholesterolemia (FH) is a genetic disease. In a heterozygous FH patient, an abnormal gene was passed on from one parent who has FH and a normal gene was passed on from the other parent. Therefore, half of the LDL receptors are absent or do not work properly and the other half are normal. Due to the fact that half of the receptors do not remove the cholesterol normally, cholesterol levels remain elevated in the blood, which further causes damage to blood vessels, blockage of arteries and heart attacks at an early age.


Today, there are an estimated 10 million individuals with FH worldwide. Premature heart disease and death in middle-aged productive men and women occurs because their FH is not diagnosed or properly treated. The National Cholesterol Education Program (NCEP) guidelines suggest children in a family with FH history be checked at age of two. There are several other genes in addition to LDLR which contribute to the causation of the disease. These include APOB, PCSK-9 etc.


The current diagnostic criteria for FH were developed by US MedPed Program, the Simon Broome Register Group in the United Kingdom, and the Dutch Lipid Clinic Network. The MedPed criteria use cut points for total cholesterol levels specific to an individual’s age and family history. The Simon Broome Register criteria for FH include cholesterol levels, clinical characteristics, molecular diagnosis, and family history. A "definite" diagnosis of FH is made if a patient has elevated cholesterol levels (>240mg/dL) and tendinous xanthomata, or if the patient has an identified mutation in the LDLR gene or APOB gene. The Dutch Lipid Clinic Network criteria assign points for family history of hyperlipidemia or heart disease, clinical characteristics such as tendinous xanthomata, elevated LDL cholesterol, and/or an identified mutation. A total point score of >8 is considered "definite" FH, 6–8 is "probable" FH, and 3–5 is "possible" FH. Simon Broome Register criteria consider a molecular diagnosis as evidence for definite FH, whilst the Dutch Lipid Clinic Network requires that at least one other criterion be met in addition to molecular diagnosis.


Although molecular diagnosis is highly recommended in all the FH Assessment Criteria and WHO guideline, however most of the conventional analyses still rely heavily on clinical assessments which are based on physical clinical examination, biochemistry analysis, imaging study (aortic stenosis/valve abnormalities, tendon xanthomas) and Lipoprotein electrophoresis but not molecular testing.


MSS FH1536™ is a novel microarray based molecular test which screens for 1536 polymorphims and mutations in 70 genes, with focus in 3 major genes, namely LDLR, APOB and PCSK9. These genes play important role in cholesterol clearance function in Lipid Metabolism. The identification of the presence of these mutations/ polymorphisms in subject's genotype establish the molecular basis to the clinical condition, therefore fills in the gap in FH Diagnosis.