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Clinical Development

Detection of Familial Hypercholesterolemia in South Africa via Cascade Screening

  • March 27, 2018

Experts in Familial hypercholesterolemia (FH) from the Medpace Central Lab were authors on a scientific poster presented at the American College of Cardiology’s 2018 Annual Scientific Session. Access the Poster here.


Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder usually resulting from mutations in the LDL receptor (LDLR) gene and less commonly from mutations in apoB100, PCSK9 or LDLRAP1. This condition is characterized by elevated levels of LDL-cholesterol (LDL-C) and premature cardiovascular disease, particularly coronary artery disease (CAD).

The heterozygous phenotype (HeFH) is characterized by elevated LDL-C levels approximately twice the normal levels (190 – 400mg/dL), tendon xanthoma and premature CAD. If untreated, the cumulative risk of a coronary event by the age of 60 years is at >50% in men and 30% in women. The homozygous phenotype (HoFH) is characterized by LDL-C levels >500 mg/dL, skin and tendon xanthoma beginning soon after birth and if untreated CAD prior to age 20 years of age. There is some overlap in the clinical phenotype between HeFH and HoFH when assessed by genotype.

FH is one of the commonest inherited diseases in the world with an estimated frequency of 1:200 to 1:250 for Caucasian populations. However in some countries such as South Africa, the prevalence in certain population groups such as the Afrikaner, Jewish and south-Asian Indians it is as high as 1:805,6, probably due to a founder effect.

In South Africa 70 to 80% of subjects of Afrikaner, Jewish or Indian origin with clinical heterozygous FH identified to date have one of 5 founder mutations – table 1. However the vast majority of FH patients remain undiagnosed and untreated and have not been screened for other mutations in the LDLR, apoB or PCSK9 genes.


One full-time and 1 part-time research nurse were hired and trained in late 2016 and beginning in January 2017 follow up of family members commenced based on index patients identified from the Wits Lipid Clinic. In the 1st 7 months, 310 family members were screened and 236 suspected FH cases identified, including black and Indian families. Demographic and LDL-C levels are shown in table 2. Genetic analysis was performed in 236 subjects suspected of FH; 130/236 (55.1%) were confirmed with a mutation consistent with FH including 16/236 (6.8%) with homozygous, compound heterozygous or double heterozygous FH.

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